Congenital cysts of the lower male genitourinary tract: a disorder with various treatment approaches and pitfalls-case report.

BACKGROUND: The cysts of the male pelvic floor represent a rare clinical entity. Their origin is linked to an altered development of paramesonephric and mesonephric ducts during embryogenesis. CASE PRESENTATION: We report our experience regarding two patients presenting cysts of the ejaculatory system treated with open and mini-invasive surgery. The patients referred to our clinic with nonspecific symptoms and the diagnosis was obtained by radiological investigations. The patient treated with an open approach developed a pelvic purulent collection and a fistula of the prostatic urethra, managed with surgical drainage and prolonged bladder catheterization. On the other hand, the patient treated with laparoscopic approach did not develop any complications. No sexual or ejaculatory disorders were reported. CONCLUSIONS: Patients with congenital cysts of the pelvic floor must be adequately informed about the risks and benefits of surgery and a careful counseling is mandatory before surgery. Treatment is recommended for symptomatic patients and an endoscopic approach is associated with a high rate of recurrence. A laparoscopic approach, when possible, is desirable.

Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study.

BACKGROUND: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. OBJECTIVE: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. INTERVENTION: The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. RESULTS AND LIMITATIONS: Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9-7.1) and median OS 20 mo (95% CI, 17-not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. CONCLUSIONS: We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. PATIENT SUMMARY: Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

Impact of multidisciplinary approach and radiologic review on surgical outcome and overall survival of patients with pancreatic cancer: a retrospective cohort study.

AIM: To evaluate the impact of multidisciplinary team case discussion including computed tomography (CT) radiologic review on surgical outcome and overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with PDAC evaluated in 2008-2011 and 2013-2016 (before and after multidisciplinary team introduction), aged <85 years and staged I-III, were included. Surgical failures and 2-year OS were compared in these periods. Available CT scans of preintervention period (2008-2011) cases were reviewed by two radiologists in consensus, assigning a resectability judgment to evaluate in how many cases a different recommendation would be achieved. RESULTS: A total of 316 patients (49.3% female, age 71±10 years) were included: 132 in 2008-2011 and 184 in 2013-2016. The proportion of patients who underwent upfront surgery was similar in the two periods (51% vs 47% in 2008-2011 vs 2013-2016). Neoadjuvant referral increased from 7% to 21% and surgical resection was excluded for 42% patients in 2008-2011 vs 33% in 2013-2016 (p = 0.002). Adjusting by age, sex, and stage, surgical failures slightly decreased in 2013-2016 (odds ratio 0.89, 95% confidence interval 0.53-1.51); the decrease was stronger when therapeutic choice complied with CT indications (odds ratio 0.76, 95% confidence interval 0.36-1.63); in both cases, the decrease could be due to chance. After correction for age, sex, and stage, the hazard ratio of 2013-2016 for OS was 0.83 (95% confidence interval 0.64-1.09). In 33/114 (29%) patients, CT retrospective review produced a change in resectability judgment. CONCLUSION: Although differences could be due to chance or generic improvement, the consistency between process and outcome indicators suggests that multidisciplinary team approach with radiologic review may improve outcomes.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Endoscopic Papillectomy for Ampullary Adenomas: Different Outcomes in Sporadic Tumors and Those Associated with Familial Adenomatous Polyposis.

BACKGROUND: Ampullary adenomas are rare and potentially malignant. Surgery was the standard treatment but endoscopic papillectomy (EP) is a possible alternative. AIM: We retrospectively evaluated the principal clinical outcomes of EP in all patients referred to our unit also dividing sporadic ampullary adenoma (SAA) from familial adenomatous polyposis (FAP)-associated adenomas. METHODS: All consecutive patients who underwent endoscopic papillectomy because of ampullary adenoma were considered. The primary outcome was the technical success of EP. Secondary outcomes included the number of procedures, the adverse event rate, the recurrence rate, the concordance of histology pre- and post-EP, and the evaluation of factors related to technical success. RESULTS: Between January 2001 and December 2015, sixty-two patients were included (21 FAP and 41 SAA). Technical success was achieved in 75.8% and was different in the two groups (FAP 95.2%, SAA 65.8%, p 0.025). Intraductal invasion was negatively associated with technical success (41.7% vs. 84.0%; p 0.005). The intestinal subtype was predictive of success (79.7% vs. 0%; p 0.012) as well as en bloc resection (90.3% vs. 61.3%; p 0.016). Adverse events were reported in 14 patients (22.6%). CONCLUSIONS: EP is an effective and safe procedure and is a viable alternative to surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03494543.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Interlaboratory concordance of p16/Ki-67 dual-staining interpretation in HPV-positive women in a screening population.

BACKGROUND: p16/Ki-67 dual staining is a candidate biomarker for triaging human papillomavirus (HPV)-positive women. Reproducibility is needed for adopting a test for screening. This study assessed interlaboratory reproducibility in HPV-positive women. METHODS: All women positive for HPV from the Italian New Technologies for Cervical Cancer 2 study, were included in this study. ThinPrep slides were immunostained for p16/Ki-67 in 4 laboratories and were interpreted in 7 laboratories. Each slide had 3 reports from different laboratories. Slides were classified as valuable or inadequate, and valuable slides were classified as positive (at least 1 double-stained cell) or negative. Interlaboratory reproducibility was evaluated with κ values. RESULTS: Overall, we obtained 9300 reports for 3100 cases; 905 reports (9.7%) were inadequate. The overall adequacy concordance was poor (κ = 0.224; 95% confidence interval [CI], 0.183-0.263). The overall positivity concordance was moderate (κ = 0.583; 95% CI, 0.556-0.610). Of the 176 cervical intraepithelial neoplasia 2+ (CIN-2+) lesions found in HPV DNA-positive women, 158 had a valid result: 107 were positive in all 3 reports (sensitivity for CIN-2+, 67.7%; 95% CI, 59.8%-74.9%), 23 were positive in 2 reports (sensitivity of the majority report, 82.3%; 95% CI, 75.4%-87.9%), and 15 were positive in 1 report (sensitivity of at least 1 positive result, 91.8%; 95% CI, 86.3%-95.5%). Thirteen CIN-2+ cases were negative in all 3 reports. The overall positivity concordance in CIN-2+ samples was κ = 0.487 (95% CI, 0.429-0.534), whereas in the non-CIN-2+ samples, it was κ = 0.558 (95% CI, 0.528-0.588). CONCLUSIONS: The p16/Ki-67 assay showed poor reproducibility for adequacy and good reproducibility for positivity comparable to that of cervical cytology. Nevertheless, the low reproducibility does not affect the sensitivity for CIN-2+.

Concordance, intra- and inter-observer agreements between light microscopy and whole slide imaging for samples acquired by EUS in pancreatic solid lesions.

BACKGROUND: No study has compared the performance of light microscopy (LM) and whole slide imaging (WSI) for endoscopic ultrasound (EUS) histological acquired tissue samples from pancreatic solid lesions (PSLs). We evaluated the concordance between LM and WSI and the inter- and intra-observer agreements among pathologists on PSLs EUS acquired samples. METHODS: LM and WSI from 60 patients with PSLs were evaluated by five expert pathologists to define: diagnostic classification, presence of a core, number and percentage of lesional cells. Washout period between evaluations was 3 months. Time of the procedures was also assessed. RESULTS: Forty-eight cell-block and 12 biopsy samples were evaluated. A high concordance between LM and WSI was found. Inter- and intra-observer agreements for diagnostic classification were substantial and complete, respectively. For all the other parameters, the inter-observer agreement was usually higher for LM. For the intra-observer, a substantial agreement was reached regarding the presence of tissue core and the number and the percentage of malignant cells. Median time for performing LM was significantly shorter than for WSI (p < 0.0001). CONCLUSIONS: LM and WSI of cell-block and biopsy samples acquired by EUS in PSLs were highly concordant, with a substantial inter-observer and a complete intra-observer agreements regarding diagnostic classification.

Primary pancreatic perivascular epithelioid cell tumor (PEComa): A surgical enigma. A systematic review of the literature.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor, with distinctive morphology and expression of myo-melanocytic markers. Current scientific literature reported just 24 cases of pancreatic PEComas. With our systematic review, we aimed at improving our understanding of the disease, focusing on the knowledge gained on epidemiology, etiology, clinical presentation, diagnosis, treatment and prognosis. METHODS: Based on the PRISMA guidelines, a systematic research was carried out on PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and EBSCO using the search terms: ("perivascular epithelioid cell tumor" OR ″PEComa") and ("pancreas "OR″ pancreatic"). RESULTS: The 4th-6th decades of life and female sex (86.9%) turned out as the most affected. Pancreatic head was the most involved site (50%), with a single lesion in almost all cases. The diagnosis was only obtained after histopathological examination (70.8%). The clinical presentation was non-specific, abdominal pain being the main symptom (60.9%). At immunohistochemistry, PEComa showed benign epithelioid predominance and a strong positivity for HMB-45, Melan-A, and α-SMA. Surgical resection was performed in almost all cases, while for one patient the multidisciplinary group chose just endoscopic and imaging follow-up, based on the benign nature of the lesion. CONCLUSIONS: The biological characteristics of pancreatic PEComa remain an enigma. Its prognosis seems to depend on whether atypical ("worrisome") histological features are available or not. Surgery turned out as the most appropriate treatment, without reaching any agreement on surgery timing. Further studies on larger population are needed to better understand the biological features of pancreatic PEComa, in order to set up guidelines in the diagnosis, treatment and follow-up.

Ki-67 cytological index can distinguish well-differentiated from poorly differentiated pancreatic neuroendocrine tumors: a comparative cytohistological study of 53 cases.

The Ki-67 labeling index has been found to bear prognostic significance in gastrointestinal neuroendocrine tumors (NETs), and it was recently incorporated in NET histological grading. Nevertheless, a reliable preoperative determination of NET grading could be useful in clinical practice. The aim of this study is to compare the results of Ki-67 labeling index, as measured on cytological samples and on surgical specimens of patients with pancreatic NETs (P-NETs). We also investigated whether concordance might be improved, using a 5 % (instead of 2 %) cutoff value for defining G2 tumors. We retrospectively identified 48 consecutive patients with 53 P-NETs, from our five institutions, and we measured Ki-67 labeling index on their cytological samples and surgical specimens. The traditional 2 % and the alternative 5 % cutoff values were used to classify G2 tumors. The concordance rate between cytological and histological grading was 46/53 (86.8 %; weighted κ statistic 0.77; 95 % confidence interval (95 % CI) 0.60-0.94). No cases of cytological G1-G2 NETs were upgraded to G3 neuroendocrine carcinoma (NEC) at histological grading. Cytology was found to be highly specific in the diagnosis of both G2 (94.1 %; 95 % CI 80.3-99.3) and G3 tumors (100.0 %; 95 % CI 92.8-100), but the sensitivity was poor for G2 NETs (66.7 %; 95 % CI 38.4-88.2) and high for the prediction of G3 NECs (100 %; 95 % CI 39.8-100.0). When the 5 % cutoff value was adopted, concordance rate was 49/53 (92.4 %; weighted κ 0.82; 95 % CI 0.64-1.00). In conclusion, Ki-67 cytological expression can distinguish well-differentiated (both G1 and G2) from poorly differentiated P-NETs, and it may be useful for their preoperative classification.

[Ejaculatory system cysts: a case report]. / Raro caso di cisti del sistema eiaculatore.

INTRODUCTION: Male pelvic floor cysts are a rare clinical entity that include: Wolffian duct remnants, Müllerian duct remnants, cysts of the seminal vesicles, prostate and ejaculatory duct/vas deferens cysts.
 CASE REPORT: We report the clinical case of a 21-year-old male patient with a history of previous surgery in childhood and more precisely: partial colectomy for congenital megacolon, removal of dysplastic right kidney and subsequent surgical adhesiolysis for bowel obstruction.
 At 17, the patient was submitted to MRI for groin pain with an incidental finding of a cystic mass at the level of the right seminal vesicle. Consequently, a TUR-ED was performed at another urology unit, for a suspected seminal vesicle ectasia, without resolution of pain symptoms. The patient was referred to us for persistent genitourinary infections, ejaculation disorder and episodes of gross hematuria. An additional MRI confirmed the presence of a cystic mass of 5,5 cm with a suspected opening into prostatic urethra. Urethrocystoscopy and urethrocystography retrograde confirmed this anatomical communication. For the persistence of the symptoms we performed retropubic surgical exeresis of the mass, with a histopathological finding of benign cyst of the vas deferens.
 Two major postoperative complications were reported: a pelvic hematoma that required surgical exploration and a urinary extravasation at the level of prostatic urethra, which resolved with prolonged urethral catheterization.
 CONCLUSIONS: Male pelvic floor cysts are a rare disease with a complex clinical and therapeutic management. A correct diagnosis is based on clinical signs and symptoms together with imaging studies of the pelvic region. The high risk of erectile dysfunction and ejaculatory disorders correlated to a surgical approach, recommend a treatment of these lesions only for symptomatic cases.

Comparison of the diagnostic accuracy of thyroid fine-needle aspiration in follicular-patterned lesions using a 5-tiered and a 6-tiered diagnostic system: a double-blind study of 140 cases with histological confirmation.

Five-tiered and 6-tiered systems for reporting thyroid fine-needle aspiration (FNA) results are used widely throughout the world. In this study, we present a double-blind study of histologically confirmed follicular-patterned neoplasms and evaluate the cytological classification of the same lesions according to both systems. One hundred and forty consecutive surgically resected thyroid follicular-patterned lesions with a diagnostic preoperative FNA were retrieved from our archive. Two cytopathologists, who were blinded to all clinical information, classified each FNA case according to their respective routine diagnostic reporting system (5-tiered or 6-tiered). Interobserver variability was assessed using Cohen's Kappa (K) coefficient. Diagnostic accuracy was determined by measuring sensitivity and specificity. Receiver operator characteristic (ROC) curves were calculated for each cytopathologist. The 140 thyroid FNAs included histologically confirmed nodular hyperplasia, follicular adenomas, follicular carcinomas, and papillary carcinomas, follicular variant (35 cases for each) obtained from 104 females and 36 males with a mean age of 48.8 years and a mean tumor diameter of 27.8 mm. Negative predictive values (PV) for benign cases were 72.2% and 68.8% in the 5-tiered and 6-tiered systems, respectively (P = 0.7009). Positive PV were 100% for malignant cases in both systems. The sensitivity (78.6% vs. 72.9%, P = 0.4305), specificity (55.7% vs. 47.1%, P = 0.3103), and diagnostic accuracy (67.1% vs. 60.0%, P =0.2143) were similar between the systems. ROC curves almost entirely overlapped (P = 0.8937). Both the 5-tiered and 6-tiered systems show similar diagnostic accuracy in follicular-patterned lesions, further supporting the adoption of a common reporting system for thyroid cytopathology.

Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study.

PURPOSE: In this report, we compared endoscopic ultrasonography (EUS), multidetector CT (MDCT), and Ga-68 DOTATOC PET/CT in patients with neuroendocrine tumors (NETs). We report our experience with use of these methods in patients suspected to have duodenopancreatic primitive NET. METHODS: Nineteen consecutive patients (mean age, 56; 21-80), who underwent both Ga-68 DOTATOC PET/CT and EUS between March 2007 and November 2008 were retrospectively included in the study (16 underwent MDCT). Suspicion of NET was confirmed by EUS-FNA and/or surgery. Operative characteristics of PET, EUS, and MDCT were compared. RESULTS: Twenty-three neuroendocrine lesions were diagnosed in 13/19 patients. EUS, PET, and MDCT correctly identified as affected 13/13 (100%), 12/13 (92%), and 10/11 (91%) patients, respectively. On a lesion basis, EUS, PET, and MDCT identified correctly as NETs 22/23 (96%), 20/23 (87%), and 13/18 (72%) lesions (P = 0.08 EUS vs. CT). Both on a patient and on a lesion basis, specificity was 67%, 83%, and 80% for EUS, PET, and MDCT, respectively. CONCLUSIONS: EUS, Ga-68 DOTATOC PET, and MDCT seem to have comparable accuracy in diagnosis of duodenopancreatic NET and their combination may allow an optimal preoperative diagnosis.

P53, bcl-2 and Ki-67 expression in adenoid cystic carcinoma of the palate. A clinico-pathologic study of 21 cases with long-term follow-up.

Adenoid cystic carcinoma (ACC) is an indolent tumor that pursues a protracted clinical course with recurrences and late metastases. The aim of this study was to investigate immunohistochemically the expression of p53, bcl-2 protein, and Ki-67 in 21 cases of ACC of the palate, all with a minimum of 10 years and a maximum of 22 years of clinical follow-up. These results were also analyzed with regard to different clinical prognoses of the histologic subtypes of ACC. High expression of p53 and bcl-2 was noted in 19 out of 21 ACC cases (90%), in which most tumor cells (from 66% to 99%) proved to be immunopositive. A relation to the histologic types, clinical staging, and survival was not found. Therefore, the high immunoreactivity against these oncoproteins in the same tumor cells suggests that these two oncogenes may be involved since the early stage of carcinogenesis. Loss of function of the p53 protein combined with bcl-2 upregulation might give the tumor cells a double growth advantage, because uncontrolled proliferation is combined with a reduced cell death rate. The interaction with other oncogenes may then trigger a multistep process able to promote tumor progression. The low labeling index Ki-67 was detected in nine out of 21 cases (42%), with a low percentage of tumor cells (from 3% to 15%) being positive, whereas the remaining 12 cases were negative. We found no relation to the histologic types, clinical staging, and survival; however, the low proliferation rate could explain the natural course of tumor.

Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma.

Breast and prostate cancer often metastasise to the skeleton. Interestingly, the histopathological characteristics of the bone lesions that arise from these two cancer types differ. Breast tumours give rise to metastases in the skeleton with a mixed lytic/sclerotic pattern, whereas a predominantly sclerotic pattern is seen in metastases from prostate tumours. Osteopontin (OPN) and bone sialoprotein (BSP) are bone matrix proteins that have been implicated in the selective affinity of cancer cells for bone. In the present study, 21 patient cases with skeletal metastasis and their respective primary tumours (12 with breast cancer, 9 with prostate cancer) were investigated by immunohistochemistry in order to assess the level of OPN and BSP. Moderate to strong OPN expression was found in 42% of all breast tumours and in 56% of all prostate tumours. Significantly more breast cancer bone metastases exhibited high OPN expression, 83%, as compared with prostate tumour bone metastases, 11% (P = 0.0019). In contrast, moderate to strong BSP expression was found in 33% of breast tumours and in 89% of prostate tumours. In the bone lesions, only 33% of breast tumour metastases showed moderate/strong BSP expression compared to 100% of prostate tumour metastases (P = 0.0046). This divergent pattern of OPN/BSP expression could be an important determinant for the different characteristics of these two types of bone metastasis, i.e., lytic vs. sclerotic, consistent with the proposed role of OPN in differentiation and activation of osteoclasts and of BSP as a stimulator of bone mineralisation.