Gorham-Stout disease: remission with sirolimus therapy.

Gorham-Stout disease (GSD) is a rare, non-hereditary, bone disease characterised by progressive osteolysis as a result of uncontrolled proliferation of endothelial-lined vessels replacing normal bone. We present a baby-girl with the classic radiological features of GSD and compatible clinical and histological findings, who developed progressive disease for over 2 years despite propranolol treatment. Propranolol treatment was stopped and sirolimus monotherapy started which resulted in near-complete resolution after 1 year, with no recurrence after discontinuation of treatment. This case not only illustrates the typical features of GSD on a variety of imaging modalities, but is also the first report showing stark contrast in response between propranolol and sirolimus treatment for GSD, highlighting how targeting lymphatic, rather than solely angiomatous, proliferation at the vascular endothelial growth factor-level may be a future direction.

Accuracy of ultrasound in the characterisation of deep soft tissue masses: a prospective study.

PURPOSE: To investigate the accuracy of ultrasound in characterising the type of mass and likelihood of malignancy in deep soft tissue masses. METHODS: Five hundred seventy-nine deep soft tissue masses were prospectively studied by ultrasound. Masses (n = 137) with prior MRI or CT were not included. Following ultrasound examination, the likely nature of the mass as well as the confidence of the reporting radiologist ('fully confident' versus 'not fully confident') about the ultrasound diagnosis was recorded. Clinical and ultrasound diagnoses were compared with the histological diagnosis which was available in 134 (23%) of the 579 masses. RESULTS: Compared with histology, clinical and ultrasound accuracy for characterising the type of mass were 47% and 88% respectively when all differential diagnoses were considered. The radiologist was fully confident regarding the type of 436 (75%) of 579 masses and, in this setting, for those cases that could be compared with histology, diagnostic accuracy was 96%. For the remaining masses, where the radiologist was not fully confident, accuracy compared with histology was 58% for the first differential diagnosis and 80% for all differential diagnoses. For identifying malignancy, sensitivity, specificity, and positive and negative predictive value of ultrasound were 97%, 58%, 67%, and 99% respectively. Ultrasound alone was considered sufficient for diagnostic workup in over half of all deep soft tissue masses. CONCLUSION: Ultrasound is useful at characterising and recognising malignancy in deep soft tissue masses. Provided local practice patterns are favourable, ultrasound may be considered a first-line investigation in the diagnostic workup of deep soft tissue masses. KEY POINTS: • In three-quarters of cases, one can be fully confident about characterising the nature of deep soft tissue masses on ultrasound and, for those fully confident cases that could be compared with histology, the diagnostic accuracy of ultrasound was 96%. • Ultrasound can correctly recognise nearly all malignant deep soft tissue masses but some benign masses will also be considered possibly malignant. • Ultrasound alone was considered sufficient for imaging workup in over half of deep soft tissue masses.

Accuracy of ultrasound in the characterization of superficial soft tissue tumors: a prospective study.

OBJECTIVE: To prospectively evaluate the accuracy of ultrasound in defining the specific nature of superficial soft tissue masses as well as determining malignancy. MATERIALS AND METHOD: Eight hundred twenty-three superficial soft tissue masses were prospectively evaluated with ultrasound by one of five experienced musculoskeletal radiologists. The radiologist at the time of examination provided one to three specific differential diagnoses and the perceived level of confidence with regard to each diagnosis. Clinical and ultrasound diagnoses were compared with the histological diagnosis to determine accuracy. Tumor malignancy was determined by histology or clinical/imaging follow-up. RESULTS: Histological correlation was present for 219 (26.6%) of the 823 masses. Compared with histology, the accuracy of clinical and ultrasound examination for determining specific tumor type was 25.6% and 81.2% respectively considering all differential diagnoses provided. Radiologists were "fully confident" with the ultrasound diagnosis in 585 (71.1%) of 823 masses overall. In this setting, when compared with histology, the diagnostic accuracy of ultrasound was 95.5%. When the radiologist was "not fully confident," accuracy was 41.3% for the first differential diagnosis and 60.9% for all differential diagnoses. Diagnostic accuracy improved with increasing radiologist experience. Sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for identifying malignant tumor were 93.3%, 97.9%, 45.2%, and 99.9% respectively. CONCLUSIONS: One can be "fully confident" at characterizing over two-thirds of superficial soft tissue masses based on ultrasound appearances and, in this setting, diagnostic accuracy is very high. Ultrasound examination is also highly accurate at discriminating benign from malignant superficial soft tissue masses.

MRI criteria for diagnosis and predicting severity of carpal tunnel syndrome.

OBJECTIVE: To study MRI criteria for diagnosing and predicting severity of carpal tunnel syndrome (CTS). METHODS: Sixty-nine wrists in 41 symptomatic CTS patients and 32 wrists in 28 asymptomatic subjects were evaluated by MRI. Circumferential surface area (CSA), flattening ratio, relative median nerve signal intensity, and retinacular bowing were measured. CTS severity was classified as mild, moderate, or severe. Parameters for patients with and without CTS and for the three severity groups were compared. ROC curves were plotted to assess accuracy for CTS diagnosis and severity prediction. RESULTS: Significant differences were found between CTS and control wrists for median nerve CSA, flattening ratio at inlet, relative median nerve signal intensity, and retinacular bowing. ROC curve analysis revealed a sensitivity, specificity, and accuracy of median nerve CSA > 15 mm2 proximal to the tunnel (CSAp) of 85.5, 100, and 90.1%. Using either CSAp or CSAd > 15 mm2 as a diagnostic criterion, MRI could achieve a sensitivity of 100% and specificity of 94% for diagnosis of CTS while overall accuracy was 98%. Significant differences were found among the three severity groups. Sensitivity, specificity, and accuracy of prediction of severe CTS using for CSAp > 19 mm2 were 75.0, 65.9, and 69.6%, respectively. CONCLUSIONS: MRI is highly accurate at diagnosing CTS and moderately accurate at determining CTS severity. We recommend using CSA > 15 mm2 either proximal to or distal to the tunnel as a diagnostic criterion for CTS and CSA > 19 mm2 proximal to the tunnel as a marker for severe CTS.

Top-Ten Tips for Imaging the Triangular Fibrocartilaginous Complex.

The triangular fibrocartilage complex (TFCC) is a crucial structure for both maintaining the stability of the distal radioulnar joint (DRUJ) and acting as a cushion for axial loading of the ulnocarpal joint. Injury to the TFCC can lead to early degeneration of the DRUJ and ulnocarpal joint, with resultant chronic wrist pain and weakness. The TFCC is a moderately complex structure with several attachments to the adjacent bony and cartilaginous structures. Familiarity with the anatomy of the TFCC is a prerequisite for identification of TFCC tears. Several pitfalls can occur while assessing the TFCC on magnetic resonance imaging (MRI) if one is not familiar with the MRI appearances. This article illustrates key tips for diagnosing TFCC tears on MRI.

MR imaging of the traumatic triangular fibrocartilaginous complex tear.

Triangular fibrocartilage complex is a major stabilizer of the distal radioulnar joint (DRUJ). However, triangular fibrocartilage complex (TFCC) tear is difficult to be diagnosed on MRI for its intrinsic small and thin structure with complex anatomy. The purpose of this article is to review the anatomy of TFCC, state of art MRI imaging technique, normal appearance and features of tear on MRI according to the Palmar's classification. Atypical tear and limitations of MRI in diagnosis of TFCC tear are also discussed.

Morphologic change in computed tomography of aldosterone-producing adenoma after radiofrequency ablation.

OBJECTIVE: To evaluate the morphologic changes of aldosterone-producing adenoma (APA) on computed tomography (CT) before and after radiofrequency ablation (RFA) and to assess the factors that are important in determining successful complete ablation of these tumours. METHOD: Between August 2004 and August 2011, 24 consecutive patients with APA undergoing CT-guided percutaneous RFA were identified from our prospective database. The pre-RFA and post-RFA CT appearances of these APAs that showed positive biochemical response were reviewed retrospectively for their 3-dimensional size, tumour volume, and CT attenuation in terms of Hounsfield units (HU). A comparison of these parameters before and after RFA was performed. RESULTS: In this study, there were 23 APAs in these 24 patients that showed biochemical cure of primary aldosteronism after RFA. When comparing post-RFA to pre-RFA CTs, there was no significant change in tumour size (14.5 mm vs 14.6 mm: P = .83) and tumour volume (1.55 cm(3) vs 1.59 cm(3); P = .41) after RFA. In nonenhanced CT images, there was no significant reduction in HU from pre-RFA to post-RFA measurements (4.4 HU vs 7.9 HU; P = .52). In contrast-enhanced CTs, there was a significant drop in HU after RFA (from 48.3 HU to 14.7 HU; P = .03). None of the included cases showed a focal region of contrast enhancement to suggest residual tumour. CONCLUSION: A change in tumour size, tumour volume, and HU in nonenhanced CT were unreliable in defining radiologic treatment success. Only changes in HU in contrast-enhanced CT was useful in confirming a positive treatment response after RFA for APA.

Intrinsic ligament and triangular fibrocartilage complex tears of the wrist: comparison of MDCT arthrography, conventional 3-T MRI, and MR arthrography.

PURPOSE: This study compares the diagnostic performance of multidetector CT arthrography (CTA), conventional 3-T MR and MR arthrography (MRA) in detecting intrinsic ligament and triangular fibrocartilage complex (TFCC) tears of the wrist. MATERIALS AND METHODS: Ten cadaveric wrists of five male subjects with an average age 49.6years (range 26-59years) were evaluated using CTA, conventional 3-T MR and MRA. We assessed the presence of scapholunate ligament (SLL), lunotriquetral ligament (LTL), and TFCC tears using a combination of conventional arthrography and arthroscopy as a gold standard. All images were evaluated in consensus by two musculoskeletal radiologists with sensitivity, specificity, and accuracy being calculated. RESULTS: Sensitivities/specificity/accuracy of CTA, conventional MRI, and MRA were 100%/100%/100%, 66%/86%/80%, 100%/86%/90% for the detection of SLL tear, 100%/80%/90%, 60%/80%/70%, 100%/80%/90% for the detection of LTL tear, and 100%/100%/100%, 100%/86%/90%, 100%/100%/100% for the detection of TFCC tear. Overall CTA had the highest sensitivity, specificity, and accuracy among the three investigations while MRA performed better than conventional MR. CTA also had the highest sensitivity, specificity, and accuracy for identifying which component of the SLL and LTL was torn. Membranous tears of both SLL and LTL were better visualized than dorsal or volar tears on all three imaging modalities. CONCLUSION: Both CT and MR arthrography have a very high degree of accuracy for diagnosing tears of the SLL, LTL, and TFCC with both being more accurate than conventional MR imaging.

Comparison of ultrasound versus fluoroscopic guided rotator cuff interval approach for MR arthrography.

Our purpose is to compare ultrasound and fluoroscopic-guided approaches to the glenohumeral joint at the rotator cuff interval for magnetic resonance (MR) arthrography of the shoulder. Forty consecutive patients were prospectively studied. 20 patients underwent ultrasound-guided and 20 patients underwent fluoroscopic guided injection. Successful rate of ultrasound guidance is 95%. No significant difference in pain score and duration of injection between two methods (P>.05). Ultrasound-guided rotator cuff interval injection of the glenohumeral joint for MR arthrography is comparable with fluoroscopic-guided injection. Ultrasound is the preferred method as there is no ionizing radiation.

Shear wave elastography of thyroid nodules in routine clinical practice: preliminary observations and utility for detecting malignancy.

OBJECTIVE: To evaluate real-time shear wave ultrasound elastography (SWE) for characterizing focal thyroid lesions in routine clinical practice. METHODS: Seventy-four patients with 81 focal thyroid lesions undergoing conventional US with needle cytology also underwent SWE. Absolute and relative SWE stiffness measurements on colour-coded elastograms were correlated with cytology and their discriminatory performances assessed. RESULTS: Seventeen nodules were malignant (13 papillary, 4 other cancers), 45 benign (43 hyperplastic nodules, 2 focal thyroiditis), 5 indeterminate ("follicular lesions"), and 5 had inadequate cytology. SWE results were higher in malignant than benign nodules (P values 0.02-0.05) although their discriminatory performances were mediocre (AUCs 0.58-0.74). The most accurate SWE cut-off, 34.5 kPa for a 2-mm region of interest, achieved 76.9 % sensitivity and 71.1 % specificity for discriminating papillary cancer from benign nodules. No thresholds produced high sensitivity without lowering specificity appreciably, and vice versa. Nodule size correlated with SWE for benign nodules (P < 0.01). Intranodular cystic change or calcification did not influence SWE. Qualitatively, elastographic artefacts and foci lacking colour elasticity signal occurred in some solid nodules. CONCLUSION: Although malignant nodules are generally stiffer than benign nodules, the precision results do not suggest a definitive role for SWE, at present, in identifying or excluding thyroid malignancy. KEY POINTS : • Shear wave ultrasound elastography (SWE) offers new insight into thyroid disease. • Papillary cancers have higher SWE indices (equating to higher stiffness) than benign nodules. • SWE appears limited in terms of identifying or excluding thyroid malignancy accurately. • Vertically aligned elastographic artefacts can occur in thyroid SWE. • Areas lacking SWE colour signal can occur in some solid thyroid nodules.

A pilot study evaluating real-time shear wave ultrasound elastography of miscellaneous non-nodal neck masses in a routine head and neck ultrasound clinic.

A pilot study was performed to evaluate shear wave ultrasound elastography (SWE) for miscellaneous non-nodal/salivary/thyroid neck lesions. Forty-six lesions undergoing conventional sonography also underwent SWE. Elastic moduli from the stiffest areas in lesions were correlated with diagnosis. Forty lesions were benign (9 lipomas, 8 lymphatic/venous vascular malformations, 7 thyroglossal duct cysts, 4 branchial cleft cysts, 4 abscesses/phlegmons, 3 neurogenic tumors and 1 each of paraganglioma, sebaceous cyst, pseudotumor, hypertrophic scar, ranula) and 6 were malignant (1 malignant fibrous histiocytoma, 2 primary squamous cell carcinomas and 3 intramuscular metastases [2 squamous cell carcinomas, 1 malignant melanoma]).Median stiffness of malignant lesions (226.4 kPa, range 55.6 to 300.0) was higher than benign lesions (28.3 kPa, range 4.0 to 300.0) (p < 0.001). SWE cut-off with highest accuracy (174.4 kPa) achieved 83.3% sensitivity and 97.5% specificity, and the cut-off with 100% sensitivity (55.6 kPa) achieved 75% specificity. All malignant lesions were suspected on conventional sonography. The preliminary data indicate that SWE is feasible for miscellaneous neck lesions. SWE would not have altered management in terms of detecting undisclosed malignancies, although as a quantitative technique, it may increase the diagnostic confidence of less experienced operators performing head and neck ultrasound.

Encephalocraniocutaneous lipomatosis: a rare case with development of diffuse leptomeningeal lipomatosis during childhood.

We describe the uncommon development of leptomeningeal lipomatosis in a girl with encephalocraniocutaneous lipomatosis (ECCL). Leptomeningeal involvement had not been present at 2 years of age, but was demonstrated on CT and MRI at 10 years of age. Our case demonstrates follow-up neuroimaging features of ECCL that may be helpful to radiologists in suggesting the correct diagnosis, as ocular and cutaneous lesions may be non-specific clinically. The developmental nature of leptomeningeal involvement in our case suggests that close clinical and radiological follow-up is important in children with suspected or established ECCL.

Shear wave elastography of focal salivary gland lesions: preliminary experience in a routine head and neck US clinic.

OBJECTIVES: To evaluate shear wave elastography (SWE) for focal lesions in major salivary glands. METHODS: Sixty lesions (49 parotid, 11 submandibular) undergoing routine ultrasound (grey scale and Doppler) also underwent SWE before US-guided needle aspiration for cytology. Quantitative indices of the shear elastic modulus (stiffness) were compared with cytological results. RESULTS: Fifty-five lesions were benign (21 pleomorphic adenomas, 18 Warthin's tumours; 16 others) and 5 malignant (2 mucoepidermoid carcinomas, 1 myoepithelial carcinoma, 1 B-cell lymphoma, 1 nodal metastasis). Shear modulus of benign lesions, median 18.3 kPa, overlapped appreciably with malignant lesions, median 13.5 kPa. However, 2 mucoepidermoid carcinomas had the highest stiffness values (81.9 kPa, 132.0 kPa). Stiffness of pleomorphic adenomas (median 22.5 kPa) was higher than Warthin's tumours (16.9 kPa) (P = 0.05 Mann-Whitney U-test). The standard deviation of stiffness values within a lesion, used as an indicator of spatial heterogeneity, was highest in mucoepidermoid cancers (median 44.2 kPa), followed by pleomorphic adenomas (median 12.4 kPa) and remaining lesions (medians 1.4-10.3 kPa). CONCLUSION: This study shows a degree of clustering of SWE indices according to pathology although it appears that SWE has suboptimal performance for ruling out malignancy, thus limiting its use in routine practice. KEY POINTS: • Shear wave elastography is a feasible technique for focal salivary gland lesions. • Elastographic artefacts aggravated by the regional anatomy may hinder this technique. • Elastographic indices vary according to pathology but there is appreciable overlap. • Overlapping indices for malignant and benign lesions limit its utility. • Pleomorphic adenomas have higher elasticity indices, i.e. are stiffer, than Warthin's tumours.

Shear wave elasticity imaging of cervical lymph nodes.

A pilot study of real-time shear wave ultrasound elastography (SWE) for cervical lymphadenopathy in routine clinical practice was conducted on 55 nodes undergoing conventional ultrasound (US) with US-guided needle aspiration for cytology. Elastic moduli of stiffest regions in nodes were measured on colour-coded elastograms, which were correlated with cytology. Malignant nodes (n = 31, 56.4%) were stiffer (median 25.0 kPa, range 6.9-278.9 kPa) than benign nodes (median 21.4 kPa, range 8.9-30.2 kPa) (p = 0.008, Mann Whitney U test). A cut-off of 30.2 kPa attained highest accuracy of 61.8%, corresponding to 41.9% sensitivity, 100% specificity and 0.77 area under the receiver operating characteristic curve. Qualitatively, elastograms of benign nodes were homogeneously soft; malignant nodes were homogeneously soft or markedly heterogeneous with some including regions lacking elasticity signal. SWE is feasible for neck nodes. It appears unsuitable for cancer screening but may detect a subset of malignant nodes. The cause of spatial heterogeneity of malignant nodes on SWE is yet to be established.

Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.

Correlation of cystoscopic impression with histologic diagnosis of biopsy specimens of the bladder.

There is a paucity of information in the contemporary literature that would permit assessment of the urologist's ability to endoscopically discriminate between benign and malignant lesions of the bladder or to predict the grade and stage of papillary neoplasms. This prospective study evaluates the correlation between cystoscopic impression of urothelial lesions and final histologic diagnoses. Sixty-four patients with 68 urothelial abnormalities requiring formal biopsy or endoscopic resection were evaluated prospectively. At the time of endoscopy, treating urologists completed questionnaires documenting the surgeon's endoscopic impression of disease type and extent and performed standard biopsy or resection of all suspicious lesions. Specimens were submitted for routine histopathologic analysis, and the results were correlated with the questionnaire data. Endoscopic evaluation correctly discriminated between dysplastic/malignant and benign/reactive lesions in this study with a sensitivity of 100%, specificity of 100%, and positive and negative predictive values of 100%. Urologists could not readily distinguish between low- and high-grade papillary urothelial lesions and were frequently unable to determine if a tumor was invasive, particularly if the degree of invasion was microscopic. Endoscopic impression at the time of bladder biopsy or resection is accurate and discriminates between the presence and absence of cancer. Endoscopic impression alone is a relatively poor staging tool with respect to extent of invasive disease and must be coupled with careful histopathologic analysis of biopsy material, bimanual examination when appropriate, and axial imaging for complete assessment of a given tumor.

A rapid postmortem cardiac troponin T assay: laboratory evidence of sudden cardiac death.

Postmortem examination may be useful in establishing the cause of sudden unexpected death. In many instances, however, limitations of staffing, budget, and time may force the pathologist to triage cases to external examination rather than autopsy. A rapid assay for cardiac troponin T (cTnT) to document suspected cardiac-related deaths may optimize the use of the time and resources of the autopsy pathologist. Peripheral blood was sampled percutaneously before each of 40 autopsies and placed in the well of the Cardiac T Rapid Assay unit in accordance with the included instructions, and the results were read after 15 minutes. The assay result, decedent age, postmortem interval, and evidence of cardiopulmonary resuscitation were tabulated and subsequently correlated with the cause of death. On final sign-out of each of the autopsies, the cause of death was determined to be cardiac-related (n = 20) versus the cause in non-cardiac control subjects (n = 20). This determination was made while the investigators were blinded to the cTnT assay result. Of the 20 cardiac deaths, 17 (85%) showed positive results for cTnT compared with 6 (30%) false-positive results among the 20 control cases; this result was statistically significant according to the chi-square test. In the over-50 age group, the sensitivity of this assay in detecting cardiac-related death was 91%, with a specificity of 86%. Perimortem cardiopulmonary resuscitation did not appear to result in false-positive results. In the appropriate setting, this rapid assay for cTnT can provide valuable data supportive of a cardiac-related death. This inexpensive test may best be used in triaging sudden deaths in persons over 50 to external examination versus complete autopsy.

Evaluation of characteristics associated with acute splenitis (septic spleen) as markers of systemic infection.

CONTEXT: Acute splenitis, also known as acute splenic tumor or septic spleen, is loosely defined as a neutrophilic infiltrate and congestion within the red pulp accompanied by splenomegaly. Standard pathology texts state that the histologic finding of acute splenitis is reflective of septic states. However, this association has seldom been tested in the medical literature. OBJECTIVE: The purpose of this study was to determine if sepsis can be predicted by the presence of quantitative characteristics used to identify acute splenitis. METHODS: The postmortem splenic tissue of 20 clinically diagnosed cases of sepsis and 20 noninfectious control cases were retrospectively examined in a blinded fashion for amount of neutrophilic infiltration, weight (obtained from autopsy report), and presence of congestion. RESULTS: No significant correlation could be found between the parameters of neutrophilic infiltrate or splenic weight and clinically diagnosed septicemia. The presence of splenic congestion was unexpectedly found to be more likely with noninfectious causes of death. CONCLUSION: Acute splenitis is presently ill defined, and no available evidence convincingly shows that its presence suggests a septic state.

Correlation of Ki-67 and p53 with the new World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia.

OBJECTIVE: The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. DESIGN: We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. RESULTS: In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. CONCLUSIONS: An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a "field effect" with occult molecular aberration.