"You just have to spread it thin": Perceptions and feeding experiences of Australian fathers of young children living with disadvantage.

The role of fathers in feeding is an emerging field within child feeding literature. Fathers have unique contributions to make to family mealtimes and child eating behaviours. However, qualitative research on fathers' experiences is limited, especially in the context of disadvantage. This study explored fathers' perceptions of their roles and feeding practices and their lived experience of disadvantage through a symbolic interactionism lens. Twenty-five Australian fathers of children aged six months to five years who experienced socioeconomic disadvantage participated in semi-structured interviews. Five themes were constructed from reflexive thematic analysis: (i) responsibilities for foodwork are based on strengths, opportunities, and values, (ii) negotiating fatherhood identity from a place of tension to acceptance, (iii) struggling with financial and mental strain, and food insecurity, (iv) managing adversity whist prioritising feeding children, and (v) paternal feeding practices are driven by values, adversity, and emotions. The division of foodwork was contingent on family capability and employment, maternal gatekeeping, paternal attitudes and values, and intergenerational, cultural and gender norms around earning and childrearing. Economic, environmental, and emotional stressors triggered changes to fathers' feeding practices, often contradicting their ideals (e.g., providing alternative meals, using rewards and electronic devices, unstructured settings). Fathers described income and food-based strategies to protect children's food intake, which may involve caregivers forgoing meals. These findings provide insight into fathers' feeding experiences through recognising personal, interpersonal, and systemic enablers and barriers. Promoting optimal feeding practices should include targeted feeding support and broader structural interventions to address inequality. Fathers' experiences as they navigate child mealtime interactions within a context of adversity can be used to inform child feeding interventions to improve child health and development.

A Rare Case of Prostatic Malakoplakia Associated with Prostate Adenocarcinoma: A Case Report and Review of Literature.

Malakoplakia is a chronic granulomatous condition that has been rarely seen affecting the prostate. Isolated malakoplakia of the prostate occurring together with prostatic adenocarcinoma is rarer still with only 9 previously recorded cases. We present a case diagnosed through needle biopsy with prostatic adenocarcinoma and then on subsequent prostatectomy was diagnosed with extensive malakoplakia occurring with the carcinoma. Patient was noted to have a urinary tract infection (UTI) 2 weeks after needle biopsy and notably, 4 of the 9 previously reported cases also presented with UTI following their biopsies. The theory that prostatic malakoplakia may be a complication of the prostate needle biopsy is logically possible, but due to the paucity in cases, it is difficult to infer causality.

Paraganglioma in The Urinary Bladder: A Pitfall in Histopathologic Diagnosis.

Paraganglioma of the urinary bladder is a rare neuroendocrine tumor which originates from the chromaffin tissue of the sympathetic nervous system. It only accounts for about 0.05% of all vesical tumors. Bladder paraganglioma may also present with non-specific symptoms which could easily lead to misdiagnosis. In this report, emphasis on the histomorphology and immunohistochemical profile of the tumor is stressed as the morphological findings could overlap with relatively more common urothelial neoplasms. Distinction from other tumors is of utter importance because of different therapeutic options. Here, we present a case of a 52 year-old, filipino, male, previously diagnosed with colonic tubulovillous adenoma, presenting with dysuria and hematuria who, after undergoing CT Stonogram revealed an incidental finding of a lobulated mass measuring 5.7 cm located at the anteroinferior portion of the urinary bladder wall.

Testicular Germ-Cell Tumors with Spermatic Cord Involvement: A Retrospective International Multi-Institutional Experience.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.

Value of liver biopsy in anorexia nervosa-related transaminitis: A case study and literature review.

Anorexia nervosa (AN) is a complex eating disorder that affects multiple organs. 60% of patients have liver injury with transaminitis. The mechanism of liver injury in AN remains unclear. We present a case of a 19-year-old female with AN was admitted to our hospital with marked transaminitis but near normal liver histology on biopsy. Her transaminitis eventually improved as she regained weight. We also conducted a literature review of similar cases to delineate the clinicopathologic spectrum of liver injury in AN patients. English published cases of adult AN patients with elevated transaminases who underwent a liver biopsy or autopsy were selected. 32 cases (including ours). All except four patients were female, with median age of 26.5 years and median body mass index 11.9 kg/m2 . Presentations mainly included hypoglycemic coma and weight loss. 63% of patients had severe transaminitis (AST >15x ULN). Other lab findings included elevated international normalized ratio (72%) and hypoalbuminemia (47%). Microscopically, all cases showed intact hepatic architecture. Fibrosis was reported in 12 cases and necroinflamfmation in 8, but only half of each had severe transaminitis. AN patients display a wide spectrum of liver histopathology which often does not correlate with the degree of transaminitis. In severe persistent AN-related transaminitis, liver biopsy is useful to assess the degree of liver injury and to exclude other potential etiologies.

Novel Modality for Neck Rejuvenation: A Prospective Multicenter Trial of Percutaneous Radiofrequency Ablation of the Cervical Branch of the Facial Nerve.

BACKGROUND: Neck rejuvenation offers few modalities of treatments limited to either invasive plastic surgery or temporary neuromodulation using botulinum toxin. OBJECTIVE: To access the efficacy, longevity, and safety of percutaneous monopolar radiofrequency (RF) ablation of the cervical branch of the facial nerve innervating the platysma for neck rejuvenation. MATERIALS AND METHODS: This prospective, multicenter trial enrolled 19 adult patients with noticeable platysmal banding at 2 different centers. All patients underwent RF ablation on the cervical branch of the facial nerve. Response was assessed immediately after treatment and then at 1, 4, 12, and 24 weeks after the procedure using photography. Masked investigators compared baseline photography and follow-up intervals to evaluate the results. RESULTS: Seventeen of the 18 patients had improvement in the platysmal banding. One patient was disqualified after ablation. Long-term sequalae such as scarring, burns, ulceration, hypopigmentation, or hyperpigmentation were not reported. CONCLUSION: The results of this multicenter study support that RF ablation of the cervical branch of the facial nerve is a novel technique that results in improvement of platysmal banding. This technique is an emerging alternative, nonsurgical option for neck rejuvenation that is relatively safe, with little downtime for the patient.

Designing Child Nutrition Interventions to Engage Fathers: Qualitative Analysis of Interviews and Co-Design Workshops.

BACKGROUND: Fathers play a pivotal role in parenting and child feeding, but they remain underrepresented in intervention studies, especially those focused on disadvantaged populations. A better understanding of fathers' experiences and needs regarding support access and child nutrition information in the context of disadvantage can inform future interventions engaging fathers. OBJECTIVE: This study aims to explore fathers' experiences; perceived enablers; and barriers to accessing support and information related to parenting, child feeding, and nutrition and to co-design principles for tailoring child nutrition interventions to engage fathers. METHODS: Australian fathers of children aged 6 months to 5 years with lived experience of disadvantage participated in semistructured interviews and co-design workshops, primarily conducted via videoconference. Creative analogies were used to guide the ideation process in the workshops. RESULTS: A total of 25 interviews and 3 workshops (n=10 participants) were conducted, with data analyzed using reflexive thematic analysis and the Capability, Opportunity, and Motivation-Behavior model. The interview data illuminated factors influencing fathers' initiation in seeking support for parenting, child feeding, and nutrition, including their experiences. It highlighted fathers' diverse information needs and the importance of an inclusive environment and encouragement. Enablers and barriers in accessing support related to parenting and child nutrition were identified at the individual (eg, personal goals and resource constraints), interpersonal (family support and false beliefs about men's caregiving role), organizational (inadequate fathering support), and systemic levels (father-inclusive practice and policy). Digital data collection methods enabled Australia-wide participation, overcoming work and capacity barriers. Videoconferencing technology was effectively used to engage fathers creatively. Key principles for engaging fathers were co-designed from the workshop data. Interventions and resources need to be father specific, child centered, and culturally appropriate; promote empowerment and collaboration; and provide actionable and accessible strategies on the what and how of child feeding. Fathers preferred multiformat implementation, which harnesses technology-based design (eg, websites and mobile apps) and gamification. It should be tailored to the child's age and targeted at fathers using comprehensive promotion strategies. CONCLUSIONS: Fathers faced barriers to accessing support and information related to parenting and feeding that may not adequately address their needs. Future interventions could integrate the co-designed principles to engage fathers effectively. These findings have implications for health service delivery and policy development, promoting father-inclusive practice.

Dads at Mealtimes: Associations between Food Security, Household and Work Chaos, and Paternal Feeding Practices among Australian Fathers Living with Disadvantage.

Understanding how fathers engage in feeding while experiencing disadvantage is important for family-focused interventions. A cross-sectional online survey involving 264 Australian fathers was conducted to explore feeding involvement and the relationships between feeding practices, food insecurity, and household and work chaos. Practices related to coercive control, structure, and autonomy support were measured for two age groups (<2 years and 2-5 years). Multivariable linear regression was used to examine the associations for each practice. Three-quarters of the sample were food insecure, impacting adults more than children, and correlated with household chaos. Food insecurity was associated with increased 'persuasive feeding' and 'parent-led feeding' in younger children. Household chaos was positively associated with coercive control practices in both younger and older child groups, with the strongest associations for 'using food to calm' and 'overt restriction', respectively. In older child groups, household chaos was negatively associated with 'offer new foods' and 'repeated presentation of new foods'. Structure practices had no significant relationships with any factors, and work chaos did not predict any feeding practices. These findings emphasize a need for societal and structural support to address food insecurity and household chaos. Tailored strategies are crucial to support fathers in responsive feeding.

GATA3 expression in paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma.

GATA3 is a zinc-finger transcription factor, which is expressed in various normal and neoplastic tissues. Amongst tumors, it labels urothelial carcinoma, collecting duct carcinoma of the kidney, breast carcinoma, lymphoma and, uncommonly, endometrial carcinoma. Few studies have investigated its positivity in various neoplasms that may mimic urothelial neoplasms. In this study, we evaluated GATA3 expression in urinary bladder paragangliomas, which may closely mimic urothelial carcinomas. We retrieved 12 cases of paragangliomas from the urinary bladder and 20 cases of paragangliomas from non-urologic sites using the Hopkins Pathology Data Base system. GATA3 was positive in 10 of the 12 (83%) urinary bladder paragangliomas studied on routine slide sections. Most (6/12) of the staining was diffusely strong (3+) staining, whereas the rest (4/12) that were positive showed mixed intensities (strong 3+ to moderate 2+). The 20 paragangliomas from other sites were constructed into tissue microarrays, wherein three cores from each tumor were taken. Fifteen out of 20 (75%) paragangliomas outside of the bladder were positive for GATA3 staining. Moderate (2+) or strong (3+) staining was seen in 13/20 (65%) of extravesical paragangliomas, ranging from 5 to 100% of the cell labeling (mean 59%, median 60%). In the remaining 7/20 (35%) cases, only weak (2/7) or negative (5/7) immunoreactivity for GATA3 was seen. An additional 15 cases of metastatic paraganglioma from various primary sites were retrieved with 12 of 15 (80%) metastatic paragangliomas staining positively for GATA3. Overall, for paragangliomas, regardless of site, 78.7% were positive for GATA3. Recognition of this finding will aid pathologists in preventing a misdiagnosis of a urothelial tumor based on GATA3 expression, which is critical given the differences in treatment, follow-up and prognosis between bladder paragangliomas and urothelial carcinoma.

Novel nonablative radio-frequency rejuvenation device applied to the neck and jowls: clinical evaluation and 3-dimensional image analysis.

OBJECTIVE: To use 3D photography to evaluate the clinical efficacy of a novel radiofrequency delivery device used to improve the appearance of rhytids and laxity of the face and neck. STUDY DESIGN: Forty-nine subjects received a total of two radio-frequency treatments to the face and neck one-month apart. The novel radio-frequency delivery device was used to heat the dermis between 41-43°C for five heat cycles. Primary outcome measures were clinical efficacy quantified by the Global Assessment Improvement Scale (GAIS) and a patient survey that assessed treatment satisfaction. RESULTS: Assessments of 3D photographs revealed an overall improvement in 74% of study subjects. 85% of patients noted an overall improvement in the appearance of their skin. 81% of patients rated their post-treatment skin laxity as improved, 85% rated their skin smoothness as improved and 62% rated their skin brightness as improved. CONCLUSION: Subjects in this study demonstrated an overall improvement in face and neck appearance with regard to skin tightening, wrinkles, and skin texture suggested by overall patient satisfaction (85%) and physician-rated GAIS improvement (74%). This study suggests that radiofrequency applied with a continuous thermal treatment device is a safe and efficacious way to improve the overall appearance of aging facial skin.

Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 µg/L at diagnosis.

BACKGROUND & AIMS: We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 µg/L at diagnosis. METHODS: We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. RESULTS: The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 µg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 µg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 µg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 µg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). CONCLUSIONS: In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 µg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with serum levels of ferritin greater than 1000 µg/L.

Single-center, open-label study of a proprietary topical 0.5% salicylic acid-based treatment regimen containing sandalwood oil in adolescents and adults with mild to moderate acne.

BACKGROUND: A proprietary topical blend of salicylic acid and highly purified sandalwood oil from Australia was used in this open-label study in adolescents and adults with mild to moderate facial acne. METHODS: The investigational regimen consisted of a foaming cleanser, an acne serum, a spot treatment, and a mask. Patients applied the treatment regimen as directed for 8 weeks. The primary efficacy measure was the percentage of patients assessed as improved, much improved, or very much improved according to the Global Aesthetic Improvement Scale (GAIS) ratings at week 8. Severity was rated using the Evaluator's Global Severity Scores (EGSS) at baseline and weeks 2, 4, and 8. Tolerability was assessed at baseline and weeks 2, 4, and 8 by asking patients to rate the severity of itching, scaling, erythema, burning, dryness, and stinging. Patients were also asked to complete an acne questionnaire. RESULTS: 89.4% (42/47) met the primary end point determined by the GAIS of improved (66%), much improved (19%), or very much improved (4%). Notable reductions in lesion counts were observed in patients with more severe or inflamed lesions. Tolerability was queried at all visits. No itching, scaling, or erythema was reported after initial application. Symptoms of intolerability peaked at week 2; however, most events were mild to moderate and were typically reported with use of the mask component. Intolerance decreased by week 4 and by week 8. The treatment regimen was well tolerated by patients. CONCLUSIONS: Results from this study support the use of a proprietary investigational regimen in patients with mild to moderate acne and warrant further investigation to determine whether longer-term therapy (ie, beyond 8 weeks) results in enhanced efficacy with minimal side effects, leading to continued patient compliance and skin improvement.

Prostate cancer: a presentation of clinicopathologic prognosticators among Filipino and American men at radical prostatectomy.

Lower incidence and mortality rates from prostate cancer (PCa) have been shown in Asian men in general compared to Westerners. This is the first study detailing the clinicopathologic features of resected prostate cancer in Filipino men living in the Philippines (PH). This study investigated the supposed "lower risk" Filipino and "higher risk" American PCa patients from the PH and the United States of America (USA), respectively. We examined 348 (176 from PH, 172 from USA) radical prostatectomy cases. The clinicopathologic features of both groups (age at time of diagnosis, preoperative prostate-specific antigen [pre-op PSA] level, Gleason score [GS], Grade groups [GG], margin involvement, extraprostatic extension [EPE], seminal vesicle invasion [SVI], and regional lymph node [RLN] metastasis) were compared. Six of seven prognosticators examined were more strongly associated with Filipinos than with Americans. Filipinos were older at diagnosis (PH: 64.32 ± 6.56 years vs USA: 58.98 ± 8.08 years) and had higher pre-op PSA levels (PH: 21.39 ± 46.40 ng ml-1 vs USA: 7.63 ± 9.19 ng ml-1). Filipino men had more advanced grade, GG 2 with minor pattern 5 (PH: 6.2% vs USA: 2.9%) and GG 5 (PH: 14.8% vs USA: 3.5%). Likewise, other adverse pathological features in margin positivity (PH: 52.3% vs USA: 23.8%), focal EPE (PH: 14.2% vs USA: 2.3%), and SVI (PH: 17.1% vs USA: 5.8%) were more commonly observed in Filipinos. This study reveals the prognostic disadvantage of Filipinos versus Americans and highlights an important difference of Filipinos from other studied Asian ethnicities that have repeatedly been shown to have lower-risk PCa. This study, the first on Filipino PCa patients with RP, suggests the need to modify Western-based risk stratification when employed in other countries like the PH.

Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey.

Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.

Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey.

PURPOSE: To survey urologic clinicians regarding interpretation of and practice patterns in relation to emerging aspects of prostate cancer grading, including quantification of high-grade disease, cribriform/intraductal carcinoma, and impact of magnetic resonance imaging-targeted needle biopsy. MATERIALS AND METHODS: The Genitourinary Pathology Society distributed a survey to urology and urologic oncology-focused societies and hospital departments. Eight hundred and thirty four responses were collected and analyzed using descriptive statistics. RESULTS: Eighty percent of survey participants use quantity of Gleason pattern 4 on needle biopsy for clinical decisions, less frequently with higher Grade Groups. Fifty percent interpret "tertiary" grade as a minor/<5% component. Seventy percent of respondents would prefer per core grading as well as a global/overall score per set of biopsies, but 70% would consider highest Gleason score in any single core as the grade for management. Seventy five percent utilize Grade Group terminology in patient discussions. For 45%, cribriform pattern would affect management, while for 70% the presence of intraductal carcinoma would preclude active surveillance. CONCLUSION: This survey of practice patterns in relationship to prostate cancer grading highlights similarities and differences between contemporary pathology reporting and its clinical application. As utilization of Gleason pattern 4 quantification, minor tertiary pattern, cribriform/intraductal carcinoma, and the incorporation of magnetic resonance imaging-based strategies evolve, these findings may serve as a basis for more nuanced communication and guide research efforts involving pathologists and clinicians.

The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.

CONTEXT.­: Controversies and uncertainty persist in prostate cancer grading. OBJECTIVE.­: To update grading recommendations. DATA SOURCES.­: Critical review of the literature along with pathology and clinician surveys. CONCLUSIONS.­: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes.

To investigate the degradation mechanism of misfolded membrane proteins from the cell surface, we used mutant cystic fibrosis transmembrane conductance regulators (CFTRs) exhibiting conformational defects in post-Golgi compartments. Here, we show that the folding state of CFTR determines the post-endocytic trafficking of the channel. Although native CFTR recycled from early endosomes back to the cell surface, misfolding prevented recycling and facilitated lysosomal targeting by promoting the ubiquitination of the channel. Rescuing the folding defect or down-regulating the E1 ubiquitin (Ub)-activating enzyme stabilized the mutant CFTR without interfering with its internalization. These observations with the preferential association of mutant CFTRs with Hrs, STAM-2, TSG101, hVps25, and hVps32, components of the Ub-dependent endosomal sorting machinery, establish a functional link between Ub modification and lysosomal degradation of misfolded CFTR from the cell surface. Our data provide evidence for a novel cellular mechanism of CF pathogenesis and suggest a paradigm for the quality control of plasma membrane proteins involving the coordinated function of ubiquitination and the Ub-dependent endosomal sorting machinery.

Spectrum of Cystic Epithelial Tumors of the Prostate: Most Cystadenocarcinomas Are Ductal Type With Intracystic Papillary Pattern.

Cystic epithelial tumors arising from the prostate are rare, and their full histologic spectrum has yet to be defined. Herein, we present 8 examples of prostatic cystic tumors including 1 giant multilocular cystadenoma and 7 cystadenocarcinomas. We divided the cystadenocarcinomas into "giant multilocular" cystadenocarcinoma (3) and "microscopic" cystadenocarcinoma (4) because of their differing clinical presentations with clinically apparent cystic masses in the former. The cystadenoma was an 11 cm multilocular cystic pelvic tumor in a 55-year-old man who presented with lower urinary tract symptoms. The cystadenoma was lined predominantly by benign acinar cells and had a distinct basal cell layer. No recurrence occurred 3 months after resection. The 3 patients with giant multilocular cystadenocarcinomas were 62 to 82 years old, had large pelvic cystic masses (up to 16 cm), and 2 presented with obstructive urinary and lower intestinal tract symptoms. One giant multilocular cystadenocarcinoma had a markedly high cystic fluid prostate-specific antigen at >80,000 ng/mL. All 3 giant multilocular cystadenocarcinomas were ductal adenocarcinoma with exuberant intracystic papillary formations. One tumor was associated with a high-grade noncystic conventional (acinar) adenocarcinoma (Gleason score 9 [ISUP grade group 5]). Follow-up on the 3 giant multilocular cystadenocarcinoma cases (7 to 21 mo) showed multiple metastases in 1 patient but was attributed to the high-grade conventional adenocarcinoma component. In addition, we described 4 examples of microscopic cystadenocarcinomas that were small (≤1 cm) solitary or multiple cystic tumors identified on pathologic examination of the prostate. In 3 of 4 microscopic cystadenocarcinomas the lining was ductal adenocarcinoma with occasional to exuberant papillae and appeared similar to the smaller cysts in the giant multilocular cystadenocarcinomas. One of the 4 microscopic cystadenocarcinomas had an acinar adenocarcinoma lining with occasional papillae and was associated with a conventional adenocarcinoma. Follow-up of the 4 patients with microscopic cystadenocarcinoma (1 to 14 mo) showed no evidence of disease. Review of literature highlighted similarities between the findings in our cases and previously published prostatic cystadenocarcinomas, including the markedly high cystic fluid prostate-specific antigen level in giant multilocular cystadenocarcinomas and the typical ductal adenocarcinoma morphology with intracystic papillary pattern. In conclusion, cystic epithelial tumors of the prostate exhibit unique clinicopathologic features. Cystadenocarcinomas, whether the clinically apparent giant multilocular form or the incidentally identified microscopic type, represent a rare underrecognized pattern of prostatic adenocarcinoma mostly within the histologic spectrum of the ductal variant.

Atypical diagnosis in prostate needle biopsies from a developing country (Philippines): The essential role of a urological pathologist.

PURPOSE: Borderline prostatic lesions, with insufficient histomorphologic features, to be definitely diagnosed as prostatic adenocarcinoma (PCa) are often signed out as "atypical glands suspicious for carcinoma" or atypical small acinar proliferation (ASAP). These findings that eventually warrant either immunohistochemical (IHC) studies or a repeat biopsy, prove to be more burdensome to patients in developing countries (such as the Philippines), where health care is not as progressive nor is it an utmost priority. At the same time, in countries like the Philippines, there is a shortage of urological pathologists. METHODS: In this study, we compared the transrectal ultrasound-guided prostate (TRUS) biopsies signed out by general surgical pathologists in St. Luke's Medical Center Quezon City from 2008-2010, and the TRUS Biopsies primarily signed out by a urologic pathologist in both St. Luke's Medical Center Quezon City and Global City from July 2013 to July 2014, and from September 2013 to July 2014, respectively. RESULTS: From 2008 to 2010, 30.6% (129 of 421) of the cases were signed out as atypical. Of these, 79 underwent IHC staining, 21 (26.6%) of which were eventually signed out as PCa. Compared to those signed out in 2013 to 2014 by our genitourinary pathologist, only 16.6% (39 of 235) of the cases were signed out as atypical. Of these, 16 underwent IHC staining, with 15 (93%) of them being definitively diagnosed as PCa. Among the 21 cases wherein a repeat biopsy was recommended, only three followed and two of these had findings of PCa on repeat biopsy. Looking at our 16.6% rate of atypicals and subtracting those that were eventually established as PCa after IHCs, our atypicals would be down to 10% (24/235) in 2013-2014 compared to 25.7% (108/421) in 2008-2010. CONCLUSIONS: These results highlight the critical role a specialist has in the field of urological pathology, especially in developing countries. It is in the diagnosis of PCa in needle biopsies that a urological pathologist impacts the use of an atypical diagnosis, by ensuring its judicious use. This ultimately benefits the patients, by lessening unwarranted expenses through the decreased dependence on IHC staining and if necessary, a repeat biopsy.