Transplant versus no transplant in myelodysplastic syndrome and acute myeloid leukemia with TP53 mutation; a referral center experience.

A remarkably high rate of post-transplant relapse in patients with TP53-mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non-HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non-HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p < .01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non-HSCT) had multi-hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non-HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow-up was 15.1 months for HSCT and 5.7 months for non-HSCT. Median disease-free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non-HSCT cohorts, respectively. Non-relapse mortality at 12 months was 22% versus 44% for HSCT versus non-HSCT. In the HSCT cohort, the rate of grade II-IV acute and chronic graft-versus-host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non-HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53-mutated MDS/AML remain an area of unmet clinical need.

Peritoneal Metastases After Intraductal Papillary Mucinous Neoplasm Resection: How Common are They?

INTRODUCTION: Peritoneal metastases (PMs) following resection of pancreatic intraductal papillary mucinous neoplasms (IPMNs) are rare. Consequently, prevalence, risk factors, and prognosis are not well known. We reviewed our institution's experience and published literature to further characterize the scope of this phenomenon. METHODS: All pancreatectomy cases (556 patients) performed at a tertiary care center between 2010 and 2020 were reviewed to identify IPMN diagnoses. Patients with adenocarcinoma not arising from IPMN, or a history of other malignancies were excluded. RESULTS: Seventy-eight patients underwent pancreatectomy with IPMN on final pathology at our institution; 51 met inclusion criteria. Of these, there were five cases of PMs (4:1 females:males). Four had invasive carcinoma arising from IPMN and one had high-grade dysplasia at the index operation. Female sex and invasive histology were significantly associated with PM (P < 0.05). PM rates by sex were 3% (95% confidence interval [CI]: 0.5-15) in males and 22% (95% CI: 9-45) in females. Rates by histology were 2.9% (95% CI: 0.5-15) for noninvasive IPMN, and 23.5% (95% CI: 9.5-47) for invasive carcinoma arising from IPMN. Median interval from surgery to PMs was 7 mo (range: 3-13). CONCLUSIONS: PMs following IPMN resection are rare but may be more common in patients with invasive histology. Although rare, PMs can arise in patients with noninvasive IPMNs. Further studies on pathophysiology and risk factors of PM following IPMN resection are needed and may reinforce adherence to guidelines recommending long-term surveillance.

Cellular Fibroma of Tendon Sheath With Novel TNC-USP6 Gene Fusion Clinically Mimicking Arthritis in a 7-Year-Old Boy.

Cellular fibroma of tendon sheath (CFTS) is a rare, benign myofibroblastic neoplasm of tenosynovial soft tissues closely resembling nodular fasciitis (NF), but is histomorphologically distinct from classic fibroma of tendon sheath (FTS). We report a case of a pediatric patient with thumb swelling clinically concerning for arthritis with a biopsy demonstrating myofibroblastic proliferation with features consistent with NF/CFTS, and molecular studies confirming the presence of a USP6 gene fusion (TNC-USP6). This case highlights a unique clinical presentation of CFTS in a pediatric patient mimicking an inflammatory or reactive/non-neoplastic musculoskeletal disorder and the increasingly crucial role of molecular testing to differentiate a reactive myofibroblastic process from a neoplasm. Moreover, this report identifies TNC as a new fusion partner to USP6 fusion partner adding to our growing understanding of the USP6-rearranged family of tumors.

Drug and Alcohol Use with Condomless Anal Sex among Men Who Have Sex with Men in Melbourne, Australia: A Retrospective Data Analysis from 2011 to 2017.

Rises in condomless anal sex among men who have sex with men (MSM) have been reported over the last decade but there is less certainty about the role that drugs, alcohol, play in this change. We examined the changes in drug and alcohol use among 22,255 MSM reporting condomless anal sex at Melbourne Sexual Health Centre in 2011-2017. There was a 7% annual increase in using drugs before and/or during condomless anal sex but a 3% annual reduction in condomless anal sex while drunk. MSM taking PrEP were more likely to report condomless anal sex with drug use (AOR: 1.21; 95%CI: 1.07-1.37) and alcohol use (AOR: 1.29; 95%CI: 1.14-1.46) compared with MSM not taking PrEP.

Bacterial Load of Chlamydia trachomatis in the Posterior Oropharynx, Tonsillar Fossae, and Saliva among Men Who Have Sex with Men with Untreated Oropharyngeal Chlamydia.

The aim of this study was to determine whether Chlamydia trachomatis could be detected in saliva and if infection is specific to an anatomical site in the oropharynx. Men who have sex with men (MSM) who were diagnosed with oropharyngeal chlamydia at the Melbourne Sexual Health Centre in 2017-2018 were invited to participate upon returning for treatment. Swabs at the tonsillar fossae and posterior oropharynx and a saliva sample were collected. Throat samples were tested for C. trachomatis by the Aptima Combo 2 assay. The bacterial loads of C. trachomatis in all samples were assessed by quantitative PCR (qPCR) detecting the ompA gene. We calculated the positivity and bacterial load of C. trachomatis for all samples. Forty-two MSM were included. The median age was 28 years (interquartile range [IQR], 24 to 33 years). Thirty-two participants (76.2%; 95% confidence interval [CI], 60.5% to 87.9%) had C. trachomatis detected by qPCR at both the tonsillar fossae and the posterior oropharynx, followed by 9.5% (n = 4; 95% CI, 2.7% to 22.6%) positive at the posterior oropharynx only and 4.8% (n = 2; 95% CI, 0.58% to 16.2%) positive at the tonsillar fossae only. Twenty-nine MSM had C. trachomatis detected in saliva (69.0%; 95% CI, 52.9% to 82.3%). The median C. trachomatis load in saliva was 446 copies/ml (IQR, 204 to 1,390 copies/ml), that in the tonsillar fossae was 893 copies/swab (IQR, 390 to 13,224 copies/ml), and that in the posterior oropharynx was 1,204 copies/swab (IQR, 330 to 16,211). There was no significant difference in C. trachomatis load between the tonsillar fossae and the posterior oropharynx (P = 0.119). Among MSM with oropharyngeal chlamydia, nearly three-quarters had chlamydia DNA detected in saliva, although the viability and implications for transmission are unknown.

A case of primary cutaneous Ewing sarcoma in a neutropenic patient.

Primary cutaneous Ewing sarcoma is a rare clinical presentation of Ewing sarcoma, usually occurring as a small, localized tumor on the extremities of young adults and associated with favorable prognosis. We report a case of primary cutaneous Ewing sarcoma, which presented on the sole of the foot of a 27-year-old patient with relapsed acute myeloid leukemia and neutropenia. Diagnosis was determined through histological features and staining, as well as fluorescence in situ hybridization and molecular testing. The patient underwent wide-local excision with plan to begin targeted chemotherapy, but unfortunately died from adenovirus pneumonia while neutropenic before targeted chemotherapy was initiated.

Antiseptic mouthwash against pharyngeal Neisseria gonorrhoeae: a randomised controlled trial and an in vitro study.

BACKGROUND: Gonorrhoea is increasing among men who have sex with men (MSM). We aimed to determine whether Listerine, a commercial mouthwash product, has an inhibitory effect against Neisseria gonorrhoeae in a randomised controlled trial (RCT) and an in vitro study, and therefore may be a potentially useful agent for gonorrhoea control. METHODS: In vitro: a suspension of ∼108 colony forming units per mL (CFU/mL) of N. gonorrhoeae was added to a serial of dilutions (up to 1:32) of alcohol-containing Listerine mouthwashes (Cool Mint and Total Care) for 1 min. A 10 µL aliquot was spread over the surface of a gonococcal agar plate and the number of N. gonorrhoeae colonies present at each dilution was calculated. The phosphate buffered saline (PBS) was used as a control. RCT: we recruited MSM with pharyngeal gonorrhoea who returned for treatment at the Melbourne Sexual Health Centre between May 2015 and February 2016. Untreated men were randomised to rinse and gargle either Listerine Cool Mint or saline for 1 min. Pharyngeal swabs were taken before and after rinsing and gargling for culture of N. gonorrhoeae. The analysis included only men who were culture positive for N. gonorrhoeae before using the allocated solution on the day of recruitment. RESULTS: In vitro: Listerine mouthwashes at dilutions of up to 1:4 for 1 min resulted in significant reduction of total N. gonorrhoeae counts but PBS has no inhibitory effect against N. gonorrhoeae. RCT: a total of 196 MSM were recruited, 58 (30%) were culture positive before using the solution. After gargling the allocated solution, men in the Listerine group were significantly less likely to be culture positive on the pharyngeal surface (52%) compared with men in the saline group (84%) (p=0.013). CONCLUSIONS: This data suggest Listerine, significantly reduces the amount of N. gonorrhoeae on the pharyngeal surface. With daily use it may increase gonococcal clearance and have important implications for prevention strategies. TRIAL REGISTRATION NUMBER: ACTRN12615000716561.

Detection of Neisseria gonorrhoeae in the pharynx and saliva: implications for gonorrhoea transmission.

OBJECTIVES: This study aimed to determine the proportion of untreated pharyngeal swabs or saliva samples positive by culture or nucleic acid amplification tests (NAATs) for Neisseria gonorrhoeae up to 14 days after an initial culture-positive pharyngeal swab. METHODS: Men who have sex with men who tested positive for pharyngeal gonorrhoea at Melbourne Sexual Health Centre (MSHC) and returned to MSHC for treatment within 14 days between 13 October 2014 and 25 March 2015 were included in this study. Pharyngeal swabs and saliva samples were collected for culture and NAAT. RESULTS: Of 33 initially culture-positive pharyngeal swabs, 32 saliva samples and 31 pharyngeal swabs were positive by NAAT and 14 pharyngeal and 6 saliva samples were positive by culture within 14 days. There was a significant decline in the proportion of repeated pharyngeal culture samples positive by culture over time (p<0.001). CONCLUSIONS: The rapid decline suggests pharyngeal gonorrhoea is short-lived, and the finding of gonorrhoea commonly in the saliva implicates this body fluid in its transmission without direct throat inoculation.

Persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea is influenced by antibiotic susceptibility and reinfection.

BACKGROUND: To guide interpretation of gonorrhea tests of cure using nucleic acid amplification testing, this study examined the persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea. METHODS: Men who had sex with men diagnosed with pharyngeal or rectal gonorrhea underwent swabbing from the pharynx or rectum 7 and 14 days following treatment. Repeat testing for N. gonorrhoeae was undertaken using real-time polymerase chain reaction (PCR) assays targeting the opa gene and porA pseudogene. RESULTS: One hundred pharyngeal and 100 rectal gonorrhea infections in 190 men were included. For pharyngeal gonorrhea, positivity of N. gonorrhoeae DNA on both PCR assays was present at days 7 or 14 in 13% (95% confidence interval [CI], 6.4%-19.6%) and 8% (95% CI, 2.7%-13.3%), respectively. For rectal gonorrhea, DNA positivity was present in 6% (95% CI, 1.4%-10.7%) and 8% (95% CI, 2.7%-13.3%), respectively. Among 200 baseline pharyngeal and rectal isolates, there were 10 with ceftriaxone minimum inhibitory concentration (MIC) ≥0.06 mg/L and azithromycin MIC ≥0.5 mg/L, of which 3 (30%) had DNA detected at day 14; among the 190 isolates with lower ceftriaxone and azithromycin MICs, only 13 (7%) had persistent DNA (odds ratio, 5.8 [95% CI, 1.3-25.4]; P = .019). One man initially infected with N. gonorrhoeae multiantigen sequence type 2400 had type 4244 infection at day 14, indicating reinfection. CONCLUSIONS: Pharyngeal and rectal gonorrhea DNA persisted in 8% of men 14 days after treatment. Persistence was associated with elevated ceftriaxone and azithromycin MICs. Persistence can also reflect reinfection.

Expression of cadherin 17 in well-differentiated neuroendocrine tumours.

AIMS: Cadherin 17 (CDH17) is expressed primarily in normal intestinal epithelium and digestive tract tumours, and has limited expression in other neoplasms. The aims of this study were to examine CDH17 expression in well-differentiated neuroendocrine tumours (WDNETs) from various primary sites, representing the foregut, midgut, and hindgut, and tumours metastasizing to the liver, and to correlate the differences between the expression of CDH17, CDX2, and thyroid transcription factor 1 (TTF1). METHODS AND RESULTS: We investigated CDH17 immunohistochemical expression in 150 primary WDNETs from eight anatomical sites, including 68 from the foregut, 70 from the midgut, and 12 from the hindgut, and 15 metastases. CDH17 immunoreactivity increased significantly from foregut to hindgut WDNETs (P < 0.0001). Pancreatic WDNETs expressed CDH17 at a significantly higher frequency than other foregut tumours. Within the midgut, appendiceal and small-intestinal WDNETs were more frequently positive for CDH17 than for CDX2. All hindgut WDNETs expressed CDH17, in contrast to CDX2 (positive in one rectal case). CDH17 expression in liver metastases was similar to that of the primary tumours. CONCLUSIONS: This study is the first to comprehensively examine CDH17 expression in WDNETs from different sites. CDH17 is a sensitive marker for midgut WDNETs, and the CDH17+/CDX2-/TTF1- phenotype was found to be sensitive (92%) and specific (91%) for hindgut WDNETs.

Esophageal eosinophilia in pediatric patients with celiac disease: is it a causal or an incidental association?

OBJECTIVES: Celiac disease (CD) and eosinophilic esophagitis (EoE) are 2 distinct disease entities affecting the gastrointestinal tract of pediatric patients. Recently it has been suggested that EoE is more prevalent in patients with celiac disease than in the general population. We studied the association between these 2 disease entities in our pediatric patients. METHODS: We reviewed our hospital files for suspected or confirmed cases of CD. Only cases with both duodenal and esophageal biopsies in pediatric patients were included. A total of 120 patients who met these criteria were included as the disease group. We also selected 100 patients with no clinical suspicion of CD and included them as a control group. Slides were reviewed using established criteria for diagnosis of both conditions. Duodenal biopsies were categorized as positive, negative, and suspicious for CD, whereas esophageal biopsies were classified as either positive or negative for esophageal eosinophilia (EE). Serologic and clinical data were additionally collected. RESULTS: Sixty-two (62) cases were considered positive for CD in the disease group; among those 4 (6.5%) showed EE. In the control group, 91 cases were negative for CD, histologically, and 7 of those had EE (7.7%). Although 6 patients in the control group were histologically suspicious for CD, none of them had evidence of EE. CONCLUSIONS: Our findings show that, in our patient population, patients with CD are not more likely to have EE than patients undergoing upper endoscopy for other reasons. Therefore, we suggest that the association between CD and EE is likely incidental and not causal.

A simple and cost-effective method of DNA extraction from small formalin-fixed paraffin-embedded tissue for molecular oncologic testing.

BACKGROUND: Extraction of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is a critical step in molecular oncologic testing. As molecular oncology testing becomes more important for prognostic and therapeutic decision making and tissue specimens become smaller due to earlier detection of suspicious lesions and the use of fine needle aspiration methods for tissue collection, it becomes more challenging for the typical molecular pathology laboratory to obtain reliable test results. We developed a DNA extraction method to obtain sufficient quantity and high quality genomic DNA from limited FFPE tissue for molecular oncology testing using a combination of H&E stained slides, a matrix capture method and the Qiagen DNA column. METHODS: THREE DNA EXTRACTION METHODS WERE COMPARED: our standard procedure of manually scraping tissue from unstained slides followed by DNA extraction using the QIAamp FFPE column (Qiagen, Valencia, CA), a glue capture method (Pinpoint Solution, Zymo Research Corp, Inc) on H&E stained slides followed by DNA extraction using either the QIAamp column or the column included with the Pinpoint kit (Zymo Research). The DNA extraction protocol was optimized. Statistical analysis was performed using the paired two-sample student's t-test. RESULTS: The combination of the matrix capture method with the QIAamp column gave an equivalent amount of DNA as our standard extraction method using the unstained slides and a 4.6-fold higher DNA yield than using the Zymo column included in the Pinpoint Slide Solution kit. Several molecular tests were performed and DNA purified using the new method gave the same results as for the previous methods. CONCLUSIONS: Using H&E stained slides allows visual confirmation of tumor cells during microdissection. The Pinpoint solution made removal of specific tissue from the slides easier and reduced the risk of contamination and tissue loss. This DNA extraction method is simple, cost-effective, and blends with our current workflow requiring no additional equipment.

Molecular characterization and survival analysis of a cohort of glioblastoma, IDH-wildtype.

Glioblastoma, IDH-wild type, the most common malignant primary central nervous system tumor, represents a formidable challenge in clinical management due to its poor prognosis and limited therapeutic responses. With an evolving understanding of its underlying biology, there is an urgent need to identify prognostic molecular groups that can be subject to targeted therapy. This study established a cohort of 124 sequential glioblastomas from a tertiary hospital and aimed to find correlations between molecular features and survival outcomes. Comprehensive molecular characterization of the cohort revealed prevalent alterations as previously described, such as TERT promoter mutations and involvement of the PI3K-Akt-mTOR, CK4/6-CDKN2A/B-RB1, and p14ARF-MDM2-MDM4-p53 pathways. MGMT promoter methylation is a significant predictor of improved overall survival, aligned with previous data. Conversely, age showed a marginal association with higher mortality. Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.

Introduction of a sexual health practice nurse is associated with increased STI testing of men who have sex with men in primary care.

BACKGROUND: The study objective was to investigate the effect of the introduction of a sexual health practice nurse on HIV and STI testing in a general practice that specialized in gay men's health. METHODS: This observational study compared the proportion of gay and other men who have sex with men (MSM) tested for HIV, syphilis, chlamydia (urethral and anal) and gonorrhoea (anal), or all of the above (defined as a complete set of tests at a single visit), two years before and one year after the nurse was introduced (Clinic A). Clinic B, a general practice which also specialized in gay men's health, but with no sexual health nurse, was used as a control. RESULTS: In Clinic A, amongst HIV negative MSM the proportion of men who had a complete set of HIV and STI tests increased from 41% to 47% (p < 0.01) after the nurse was introduced. Amongst HIV positive MSM attending clinic A there was an increase in the proportion of men who had a complete set of tests after the nurse was introduced from 27% to 43% (p < 0.001). In Clinic B there was no significant increase in testing in the proportion of either HIV negative or HIV positive men who had a complete set of tests over the same time periods. CONCLUSIONS: The introduction of the sexual health practice nurse resulted in significant increases in episodes of complete STI testing among MSM. The effect was most pronounced among HIV positive MSM.

MRI of pregnancy-related issues: abnormal placentation.

OBJECTIVE: In this article, we review the clinical significance of abnormal placentation and the role of MRI in diagnosis and management of this potentially morbid condition. We present our clinical perspective on diagnosing this challenging problem with MRI and review the imaging findings that can lead to a correct diagnosis. CONCLUSION: As abnormal placentation becomes more prevalent, in large part due to the markedly rising rates of cesarean delivery, there is a need for accurate antenatal diagnosis of this condition to prevent maternal morbidity and mortality. Maternal and fetal outcomes can be optimized through multidisciplinary planning to achieve accurate diagnosis and anticipation of the extent of abnormal placentation in the antenatal period. Imaging findings of abnormal placentation have been described for both ultrasound and MRI, although limitations exist for each technique. Although ultrasound remains the primary screening modality for the detection of abnormal placentation, MRI is a complementary technique that should be considered when ultrasound is inconclusive or incomplete. Familiarity with MRI techniques to assess the placenta, MRI appearance of normal placenta, and imaging findings that suggest abnormal placentation can help radiologists contribute to a successful maternal outcome.

Molecular Pathology Education: A Suggested Framework for Primary Care Resident Training in Genomic Medicine: A Report of the Association for Molecular Pathology Training and Education Committee.

Developments in genomics are profoundly influencing medical practice. With increasing use of genetic and genomic testing across every aspect of the health care continuum, patients and their families are increasingly turning to primary care physicians (PCPs) for discussion and advice regarding tests, implications, and results. Yet, with the rapid growth of information, technology, and applications, PCPs are finding it challenging to fill the gaps in knowledge and support the growing needs of their patients. A critical component in expanding PCP genomic literacy lies in the education of physicians in training and in practice. Although a framework for developing physician competencies in genomics has already been developed, the Association for Molecular Pathology is uniquely situated to actively utilize the skills of its members to engage and support PCPs in this effort. This report provides an overview and a suggested basic teaching framework, which can be used by molecular professionals in their individual institutions as a starting point for educational outreach.

Adding to the Allied Health Student Experience: Motivators, Deterrents, and How to Get More from Peer Teaching.

Volunteering as a peer tutor offers teaching experience to allied health students who will one day teach patients and colleagues. It also provides an opportunity for students to extend themselves personally and academically. Medical and nursing literature supports peer teaching, yet fewer publications describe the experience of allied health students. This study investigated the effects of cross-level peer tutoring in anatomy, for the peer tutors and their students. Peer tutors revealed their primary concern as lacking anatomical knowledge; however, students valued the currency of their student experience and the opportunity to discuss learning processes with a peer. Recommendations from peer tutors and students included: recognition of the value of interactions between students and peer tutors; value of teaching how to learn, rather than content; and for academics to introduce peer tutors as peers, which clarifies the students' expectations of the peer tutor.

Impact of routine mismatch repair screening on genetic counseling and surgical management in colorectal cancer patients.

BACKGROUND: Mismatch repair (MMR) deficiency in colorectal cancer (CRC) should prompt consideration of genetic counseling (GC) as a Lynch syndrome (LS) diagnosis may have several implications for the patient and family. The study aims were to examine how routine MMR testing influences the rate of GC and surgical resection extent. METHODS: A single-institution retrospective review was performed on CRC specimens (including colonoscopic biopsies) routinely screened for MMR deficiency from 2012 to 2018. MLH1-deficient cancers with mutated BRAF or MLH1-promoter hypermethylation were excluded. RESULTS: MMR deficiency was identified in 295 of 1139 CRC specimens. After exclusions, 57 patients remained. Forty-two patients (74%) were identified preoperatively, and 35 (83%) were referred to GC: 16 were seen preoperatively, 9 postoperatively. Eight patients were diagnosed with Lynch syndrome (LS) preoperatively: 2 had no resection, 2 underwent segmental resection and 4 underwent extended resection. CONCLUSIONS: Most MMR-deficient patients were identified and referred to GC preoperatively, though not all were seen. Of the preoperatively diagnosed LS patients, half underwent extended resection. Barriers to GC and decision-making around resection extent bears further study.

A Curriculum for Genomic Education of Molecular Genetic Pathology Fellows: A Report of the Association for Molecular Pathology Training and Education Committee.

Molecular genetic pathology (MGP) is a subspecialty of pathology and medical genetics and genomics. Genomic testing, which is defined as that which generates large data sets and interrogates large segments of the genome in a single assay, is increasingly recognized as essential for optimal patient care through precision medicine. The most common genomic testing technologies in clinical laboratories are next-generation sequencing and microarray. It is essential to train in these methods and to consider the data generated in the context of the diagnosis, medical history, and other clinical findings of individual patients. Accordingly, updating the MGP fellowship curriculum to include genomics is timely, important, and challenging. At the completion of training, an MGP fellow should be capable of independently interpreting and signing out results of a wide range of genomic assays and, given the appropriate context and institutional support, of developing and validating new assays in compliance with applicable regulations. The Genomics Task Force of the MGP Program Directors, a working group of the Association for Molecular Pathology Training and Education Committee, has developed a genomics curriculum framework and recommendations specific to the MGP fellowship. These recommendations are presented for consideration and implementation by MGP fellowship programs with the understanding that MGP programs exist in a diversity of clinical practice environments with a spectrum of available resources.

A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy.

PURPOSE: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. METHODS AND MATERIALS: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. RESULTS: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. CONCLUSIONS: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.