Update on aneurysmal bone cyst: pathophysiology, histology, imaging and treatment.

Aneurysmal bone cyst (ABC) is a benign but locally aggressive lesion that predominantly affects children and young adults. ABC, which accounts for approximately 70% of the cases, is now recognized to be a true neoplasm, whereas ABC-like changes associated to other bone neoplasms (also referred in the literature as secondary ABC) accounts for the remaining 30%. The solid variant of ABC is also considered a true neoplasm but is rare. ABC can involve any bone in the body, and although it has a metaphyseal preference, it can involve any part of a bone and soft tissues. As with any bone tumor, the initial evaluation of ABCs should be done with radiographs followed by magnetic resonance imaging or less frequently computed tomography for further characterization. The imaging appearance of ABC is variable; however, a lytic and expansile lesion with fluid-fluid levels is the most common presentation. The main differential diagnosis of an ABC in the pediatric population is unicameral bone cyst (UBC) and telangiectatic osteosarcoma, therefore a biopsy is recommended before treatment. The therapeutic options of ABC range from curettage with or without adjuncts such as phenol, liquid nitrogen, argon laser and bone grafting or bone substitutes to more recently employed alternatives such as image-guided sclerotherapy with various sclerosing agents and monoclonal antibodies (e.g., Denosumab).

Pediatric intracranial neurenteric cyst of the oculomotor nerve: a case-based review.

BACKGROUND: Neurenteric cysts (NECs) of the central nervous system (CNS) are uncommon congenital entities arising from embryonal elements. Intracranial NECs in the pediatric population are rare. METHODS: The authors describe the presentation, radiographic imaging, and pathologic findings of an 11-year-old boy with a right oculomotor nerve NEC. A literature review was performed to identify additional cases of pediatric intracranial NECs published in the English language, over the past 30 years (1990-2020). The authors discuss the presentation, investigations, management, and prognosis of this interesting entity. RESULTS: We describe an 11-year-old boy who presented to neurosurgical attention with disconjugate gaze, anisocoria, and ptosis. Magnetic resonance imaging (MRI) demonstrated a lobulated, cystic, and peripherally enhancing mass involving the right oculomotor nerve. The patient underwent pterional craniotomy for drainage of the cyst and subtotal resection of the cyst wall. The tan-colored mass was displacing the basilar artery, compressing the cerebral peduncle, and adherent to the inferior surface of the tentorium. The lesion was within the oculomotor nerve and splitting the fibers, and the cystic contents were thick and mucinous. Histopathological examination of the specimen demonstrated a thin fibrous cyst wall with scattered inflammatory cells and lined by simple columnar epithelium containing mucin. The lining cells were immunoreactive with epithelial membrane antigen (EMA) and pan-keratin AE1/AE3. The diagnosis of a NEC was rendered. A comprehensive literature review of pediatric intracranial NECs yielded 46 additional lesions published in the literature, involving the skull base, posterior fossa, cerebral convexity, and cranial nerves. NECs present with local mass effect and less commonly, with aseptic meningitis or intracystic hemorrhage. Maximal safe GTR remains the mainstay management, although cyst drainage and marsupialization, cyst shunting, and fenestration of cystic contents into the ventricle or basal cisterns have been reported with variable success. CONCLUSION: CNS NECs are rare congenital entities; although they occur less frequently in the intracranial components compared to the spine, their diagnosis and management should be considered for intracranial cystic lesions. Maximal safe GTR is the mainstay treatment and frequently yields favorable outcomes.

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach in a Hispanic Pediatric Patient With APC Gene Variant c.-191T>G.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare gastric polyposis syndrome defined by numerous polyps (>100) in the fundus and body of the stomach with sparing of the lesser curvature and antrum. GAPPS is linked to a variant in the promoter 1B region of the APC gene. These variants carry a high risk of developing gastric adenocarcinoma, which can occur at an early age. We report a case of GAPPS discovered in a 16-year-old Hispanic girl after endoscopy detected extensive fundic gland polyposis. Genetic testing revealed a promoter 1B point mutation of the APC gene, variant c.-191T>G. Although similar variants have been reported (i.e., c.-191T>C, c.-195A>C, c.-192A>G) in association with GAPPS, variant c.-191T>G has not nor has GAPPS ever been described in a Hispanic individual before.

Three Distinct Vascular Anomalies Involving Skeletal Muscle: Simplifying the Approach for the General Radiologist.

Venous malformations and hemangiomas of the skeletal muscle are separate entities with different clinical presentation, histology, and imaging findings. Recent advances in the field of vascular anomalies and current efforts in the unification of terminology by the International Society for the Study of Vascular Anomalies are pivotal in understanding and differentiating intramuscular venous malformations and intramuscular capillary-type hemangioma. Fibroadipose vascular anomaly is another recently defined vascular anomaly affecting the skeletal muscle, with a distinct clinical presentation, histology, and imaging appearance. These 3 distinct vascular anomalies are reviewed and their histologic features, clinical presentation, imaging appearance, and treatment are discussed.

A Comprehensive Analysis of the Association Between Gleason Score at a Positive Surgical Margin and the Risk of Biochemical Recurrence After Radical Prostatectomy.

Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.

A unique presentation and rare pathological finding for urachal sinus.

We report an otherwise well developing 2-year-old girl who presented with a urachal sinus with its opening located at the midline between umbilicus and the pubic symphysis. Diagnosis was made by ultrasound preoperatively, and confirmed during surgery. Additionally, columnar epithelium was found in the portion of sinus tract traversing the abdominal wall. Metaplasia of the sinus tract is worrisome, as urachal carcinomas have been traditionally characterized to result from this process.

Lack of Association between COX-2 Staining Level and Biochemical Recurrence Following Salvage Radiation Therapy for Recurrent Prostate Cancer.

OBJECTIVE: The ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer following radical prostatectomy has potential for improvement. Cyclooxygenase-2 (COX-2) overexpression has previously correlated with poor clinical outcomes following primary treatment for prostate cancer, however its predictive ability in the specific setting of SRT has not been examined to date. This study evaluated the association between COX-2 staining intensity and BCR following SRT for recurrent prostate cancer. METHODS: We utilized a cohort of 151 patients who underwent SRT between July 1987 and July 2003. COX-2 staining intensity in primary tumor samples was detected using monoclonal antibodies and quantified using a computer-assisted method. The association between COX-2 staining intensity and BCR was evaluated using multivariable Cox regression models. RESULTS: When examining COX-2 staining level as three-level categorical variable (low, moderate, high) based on approximate sample tertiles, there was no evidence of an association with BCR (P=0.18). More specifically, in comparison to patients with low staining intensity, there was no significant difference in risk of BCR for moderate (Relative risk [RR]: 1.17, P=0.56) or high (RR: 0.72, P=0.22) COX-2 staining intensity patients. This lack of association was also observed when considering COX-2 staining intensity as a continuous variable (RR: 0.83, P=0.15). CONCLUSION: Our results indicate that COX-2 staining intensity is likely of little use in discriminating prognosis of SRT. It appears that the search for prognostic factors associated with BCR should continue elsewhere in order to further enhance patient selection for SRT.

Comparative validation of nomograms predicting clinically insignificant prostate cancer.

OBJECTIVE: To validate and compare the accuracy and performance of nomograms predicting insignificant prostate cancer and to analyze their performance in patients with different cancer locations. METHODS: Our cohort consisted of 370 radical prostatectomy patients with Gleason ≤6 prostate cancer diagnosed on transrectal biopsy with at least 10 cores. We quantified the performance of each nomogram with respect to discrimination, calibration, predictive accuracy at different cut points, and the clinical net benefit. We also evaluated these parameters in subgroups of patients with predominantly anterior-apical (AA) and posterior-basal (PB) tumor location. RESULTS: Insignificant prostate cancer was present in 141 patients (38%). The Kattan and Steyerberg nomograms outperformed other studied models and demonstrated fair discrimination (areas under the receiver operating characteristics curve 0.768 and 0.770, respectively), good calibration, balanced predictive accuracy, and the highest net benefit. All nomograms were less accurate at higher levels of predicted probability. The performance of the nomograms was better in patients with PB tumors than in those with AA tumors. The loss of correlation with the actual prevalence of insignificant prostate cancer at higher levels of predicted probability was not seen in the PB subgroup but was particularly noticeable in the AA subgroup. CONCLUSION: The Kattan and Steyerberg nomograms demonstrated the best performance in predicting the probability of insignificant prostate cancer in a contemporary cohort of patients with Gleason ≤6 cancer diagnosed on specimens from an extended transrectal biopsy. However, all studied nomograms were more accurate in identifying significant rather than insignificant disease, particularly for tumors located in the apical and anterior prostate.

Partial sampling of radical prostatectomy specimens: detection of positive margins and extraprostatic extension.

Currently there is no global agreement as to how extensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)-2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 patients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to alternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid-anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid-anterior aspects, supplemented by the remaining ipsilateral anterior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Prognostic implications of partial sampling of radical prostatectomy specimens: comparison of 3 methods.

PURPOSE: We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens. MATERIALS AND METHODS: The study group consisted of 1,499 patients treated with radical prostatectomy. All specimens were processed uniformly and submitted entirely. For each patient with a positive margin or extraprostatic extension we determined whether these pathological characteristics would have been diagnosed had the specimen been examined by 3 partial sampling techniques. The Harrell concordance index was used to quantify the predictive performance of the Cox models based on the potential findings of the different sampling methods. RESULTS: Partial sampling methods 1 and 2, which included the examination of alternate slides, missed 13% to 21% of positive margins and 27% to 46% of extraprostatic extensions. The effect on biochemical recurrence-free survival of these undetected pathological features was similar to that of positive margins and extraprostatic extension that would have been diagnosed by corresponding techniques. Method 3, which sampled the entire posterior region, the mid anterior prostate and the rest of the ipsilateral anterior gland (if sizeable tumor was seen), detected 95% of positive margins and 94% of extraprostatic extensions. The extraprostatic extension missed by this method was not associated with a significant increase in the risk of biochemical recurrence. The Harrell concordance index of the multivariate models was 0.806, 0.797, 0.795 and 0.804 based on the results of complete sampling, and methods 1, 2 and 3, respectively. CONCLUSIONS: Examining alternate sections of prostatectomy specimen results in missing clinically important positive margins and extraprostatic extension. It decreases our ability to predict biochemical recurrence-free survival.

Prostate cancers of different zonal origin: clinicopathological characteristics and biochemical outcome after radical prostatectomy.

OBJECTIVE: To evaluate the effect of prostate cancer zonal origin on the biochemical outcome after radical prostatectomy, to analyze clinicopathological features of tumors arising in different zones and to test the ability of the nomogram to predict the probability of transition zone cancer at radical prostatectomy. METHODS: Our cohort consisted of 1441 patients who underwent radical prostatectomy who did not receive neoadjuvant treatment. Clinicopathological characteristics and biochemical outcomes were compared between the groups of men with different zonal location of prostate cancer. Performance of the nomogram in predicting cancer location was evaluated with respect to discrimination and calibration. RESULTS: The rates of positive margin were similar in men with transition zone and mixed tumors and were significantly higher than those with peripheral zone tumors. Most of the positive margins in patients with transition zone and mixed cancers were located at the apico-anterior part of the gland. On multivariate analysis, transition zone cancer location was associated with better biochemical recurrence-free survival (P = .043). The Harrel c-index of the models that did and did not include zonal origin of cancer was 0.810 and 0.807, respectively. Performance of the nomogram was poor. CONCLUSION: The association between transition zone tumor origin and the risk of biochemical recurrence does not add important predictive value to the standard prognostic factors. Although information about the risk of prostate cancer involvement of the transition zone may be important for surgical planning, our ability to predict this risk preoperatively is limited.

Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols.

BACKGROUND: Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs. OBJECTIVE: To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy. DESIGN, SETTINGS, AND PARTICIPANTS: The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤ 6 on transrectal biopsy with ≥ 10 cores. INTERVENTION: Radical prostatectomy without neoadjuvant treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤ 6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared. RESULTS AND LIMITATIONS: A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols. CONCLUSIONS: Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer.

Tumor focality is not associated with biochemical outcome after radical prostatectomy.

BACKGROUND: The clinical and prognostic significance of unifocal prostatic carcinoma is not clearly understood. In the current study, we sought to characterize the clinical and pathologic characteristics of unifocal and multifocal prostate cancers and to investigate the effects of tumor focality on biochemical outcome after radical prostatectomy. METHODS: Our analysis included 1,444 radical prostatectomy patients with available information concerning the number and location of tumor foci in the specimen. Each patient was assigned to one of three groups depending on whether they had unifocal, multifocal, or extensive cancer. Clinical and pathological features as well as biochemical outcomes were compared between the groups. RESULTS: Two hundred and seventy-two mens in the study cohort (18.8%) had unifocal cancer. The rates of unifocal cancer did not differ significantly between the three studied time intervals (17.3% in 1992-1998, 20.5% in 1999-2004, and 17.8% in 2005-2011). The number of positive biopsy cores was slightly lower in the unifocal group, while the overall amount of biopsy tissue containing cancer was similar in both groups. The patients in the multifocal group had higher pathologic Gleason scores, increased incidence of positive surgical margin, and larger tumors. The rate of clinically significant Gleason score upgrade was significantly higher in the multifocal group compared to the unifocal group (35.7% vs. 21.7%, respectively, P < 0.001). The biochemical outcome after radical prostatectomy did not differ between patients with unifocal and multifocal cancers both on univariate and multivariate analyses. CONCLUSIONS: Tumor focality is not an independent prognostic factor of biochemical outcome in radical prostatectomy patients.

Clinically significant Gleason sum upgrade: external validation and head-to-head comparison of the existing nomograms.

BACKGROUND: Several nomograms have been developed for the purpose of predicting the likelihood of an increase in Gleason sum (GS) from biopsy information compared with the GS determined after examination of the "entire prostate" in patients with prostate cancer. In this study, the authors evaluated and compared the ability of 4 nomograms (published by Capitanio et al, Chun et al, Kulkarni et al, and Moussa et al) to predict GS upgrades for patients with biopsy GS ≤6 prostate cancer who underwent radical prostatectomy (RP) at their center. METHODS: The entire study cohort included 942 patients with a biopsy GS ≤6. Predictive performances of the nomograms were compared using area under the receiver operating characteristic curve (AUC-ROC) analysis, calibration plots, and decision curve analysis (DCA) in the entire cohort, in patients with low-risk prostate cancer (LRPC), and a subgroup of those patients who underwent extended biopsy with ≥10 cores. RESULTS: Patients with a GS ≥7 at prostatectomy included 319 of 942 patients (33.9%) in the entire study cohort, 263 of 814 patients (32.2%) with LRPC, and 84 of 301 patients (27.9%) with LRPC who underwent extended biopsy. With an AUC-ROC of 0.637 to 0.647 in the different subgroups of patients with low-risk cancer, the Kulkarni et al nomogram demonstrated significantly higher discriminative ability compared with the other nomograms. The same nomogram provided a small clinical benefit at DCA. All nomograms were poorly calibrated. CONCLUSIONS: The available prognostic tools had limited ability to predict clinically significant upgrading in patients with biopsy GS ≤6 and, thus, the authors concluded that these tools are not ready for clinical application.

Prostate sampling by 12-core biopsy: comparison of the biopsy results with tumor location in prostatectomy specimens.

OBJECTIVE: To analyze the diagnostic performance of individual prostate biopsy cores. The 12-core transrectal prostate biopsy scheme has emerged as a standard of care. However, quality of sampling may vary in different areas of the prostate included in this procedure. MATERIAL AND METHODS: Two-hundred fifty men underwent radical prostatectomy at our institution. All participants had a systematic 12-core transrectal prostate biopsy containing lateral and medial cores from each side of the apical, medial and basal thirds of the prostate. Biopsy results were matched with histologic maps of the prostatectomy specimens. Sensitivity, negative predictive value (NPV), and overall accuracy were calculated for each biopsy core location and compared between different groups of cores. In addition, patients in the upper quartile of prostate weight were compared with the rest of the cohort. RESULTS: Sensitivity, NPV, and overall accuracy were significantly lower for apical cores. Average NPV and overall accuracy of basal and mid-lateral biopsies were inferior to those of medial biopsies on the same levels. However, sensitivity of these lateral cores was similar to that of the medial cores. Sensitivities of apical and mid cores were significantly lower in patients with larger prostates. CONCLUSION: Decreased accuracy in lateral mid- and basal cores results from higher frequencies of cancer in corresponding prostate areas, and therefore additional samples should be taken at these locations. In addition, diagnostic accuracy of apical cores may be improved through better targeting of the prostatic apex. This may be particularly important in patients with larger prostates.

Severe colitis associated with docetaxel use: A report of four cases.

Diarrhea is a common side effect of chemotherapy. Pseudomembranous colitis is a well known complication of antibiotic treatment that can also be observed, albeit rarely, with certain chemotherapeutic agents. We present four cases of severe colitis in patients undergoing treatment with taxane-based chemotherapy for pancreatic, lung and breast cancer. None of them had recently received antibiotics. One patient presented with a bowel perforation and three had endoscopic findings of pseudomembranous colitis. Two of these three patients had negative stool toxin assays for Clostridium difficile. In the patient presenting with perforation, an emergency left hemicolectomy was performed and the pathological findings in the colon were acute inflammation and ischemic necrosis; the other three patients were treated with oral vancomycin and/or oral or intravenous metronidazole leading to complete resolution of the symptoms. Apart from pseudomembranous colitis, we describe patients presenting with neutropenic enterocolitis as well as ischemic colitis after docetaxel use. These cases provide some insight into the spectrum and varied clinical presentations of severe colitis associated with taxane-based chemotherapy.