Risks, Benefits, and Effects on Management for Biopsy of the Papilla in Patients With Familial Adenomatous Polyposis.

BACKGROUND & AIMS: Ampullary and duodenal cancer are the leading causes of death in patients with familial adenomatous polyposis (FAP) after colectomy has been performed. Risk of duodenal cancer is determined based on Spigelman stage (SS) of duodenal polyposis. Guidelines recommend endoscopic surveillance of the duodenum and visualization of the papilla to stage duodenal polyposis. There is no consensus on whether biopsies should be routinely collected from duodenal papilla and findings included in SS. Additionally, there are no data on the risk of pancreatitis after biopsy collection from papilla of patients with FAP. We studied the incidence of pancreatitis after biopsy of the papilla in patients with FAP and effects of biopsy findings on SS. METHODS: We identified consecutive patients with FAP at a single center from January 2011 through December 2018 with ≥1 endoscopy with biopsy of the papilla. Patients with history of foregut surgery were excluded. We identified 273 patients with FAP who had biopsies collected from papilla over 792 EGDs, with 1-8 independent exams with biopsy per patient. We collected demographic, endoscopic, and histology data from patients and calculated SS with vs without biopsy findings. Post-procedural pancreatitis was defined by 2 of the following: abdominal pain, lipase level 3-fold the upper limit of normal, or radiography findings consistent with pancreatitis within 7 days of esophagogastroduodenoscopy (EGD). RESULTS: Pancreatitis developed in 2 patients (0.73%): 1 after biopsy of a normal-appearing papilla and 1 after biopsy of an abnormal appearing papilla. Inclusions of biopsy data increased SS in 36 patients (13.2%), with consideration of prophylactic duodenectomy for 3.3%. CONCLUSIONS: Pancreatitis after biopsy of the duodenal papilla is rare. Histology data obtained from biopsy of the papilla in patients with FAP can change SS and affect patient management.

PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma).

BACKGROUND: The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high-risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features. METHODS: Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma. RESULTS: Eight-eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P < 0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC-P had the highest relative risk (4.993, 95% confidence interval, 3.451-7.223, P < 0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present. CONCLUSIONS: PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC-P. This is the first study showing the association of PTEN loss with stromogenic PCa.

Atypical intraductal proliferation and intraductal carcinoma of the prostate on core needle biopsy: a comparative clinicopathological and molecular study with a proposal to expand the morphological spectrum of intraductal carcinoma.

AIMS: Atypical intraductal proliferation (AIP) of the prostate is histologically worse than high-grade prostate intraepithelial neoplasia, but lacks the diagnostic criteria of intraductal carcinoma of the prostate (IDC-P). The aim of this study was to compare the clinicopathological and molecular characteristics (ERG overexpression and PTEN loss) of AIP and IDC-P in core needle biopsies. METHODS AND RESULTS: One hundred and six [84 (5.6%) of 1480 consecutive and 22 retrospectively collected] cases met the criteria: AIP only (2.4%), IDC-P only (1.3%), and IDC-P coexisting with AIP (2%). Invasive adenocarcinoma [prostate adenocarcinoma (PCa)] was present in 96% and 97% cases of AIP and IDC-P, respectively. The mean number of glands/focus and the largest gland diameter for AIP and IDC-P were 7.6 (range, 2-27) and 11.7 (range, 1-51), and 0.59 mm (range, 0.2-1.1 mm) and 0.75 mm (range, 0.2-1.8 mm), respectively. For AIP, loose cribriform architecture was the most common (93%) morphology. IDC-P-associated PCa had more aggressive pathology, including the highest combined Gleason score (GS), high-grade GS ≥ 4 + 3, and largest percentage involvement of core by PCa and percentage positive cores, than AIP-associated PCa (P < 0.05). Within the AIP group, ERG status and PTEN status were similar to those of adjacent PCa in 97% and 88% of cases, respectively. Within the IDC-P group, ERG status and PTEN status were similar among IDC-P, AIP and PCa in 96% and 91% of cases, respectively. PTEN loss was frequently heterogeneous in PCa, and localized adjacent to AIP or IDC-P. CONCLUSIONS: AIP represents a lower-grade morphological spectrum of IDC-P, associated with intermediate-risk PCa. Patients with only AIP need an immediate repeat biopsy to rule out clinically significant PCa.

A need to reconsider guidelines on management of primary spontaneous pneumothorax?

BACKGROUND: The key guidelines in the management of primary spontaneous pneumothorax (PSP) include the 2010 British Thoracic Society (BTS) Pleural Disease guideline and 2001 American College of Chest Physicians (ACCP) Consensus Statement. Current recommendations are dependent on radiographic measures which differ between these two guidelines. The aim of this study is to compare size classification of PSP cases, according to BTS and ACCP guidelines, and to evaluate guideline compliance. FINDINGS: We conducted a retrospective evaluation of all PSP episodes presenting to St Thomas' Hospital, London, between February 2013 and December 2014. Data was recorded from review of chest X-rays and patient records. Eighty-seven episodes of PSP in 72 patients were identified (median age 25 years, IQR 22-32.25). Classification of "large" and "small" showed the greatest disparity in those managed conservatively (12/27, 44%) or with aspiration only (11/23, 48%). In this UK study, BTS guidelines were followed in 70% of episodes with adherence to ACCP guidelines in 32% of episodes. CONCLUSIONS: There is a poor agreement in size classification between BTS and ACCP guidelines, resulting in conflicting recommendations for management of PSP. Robust clinical trial evidence is required to achieve international consensus on the management of PSP.

Improvement of diagnostic agreement among pathologists in resolving an "atypical glands suspicious for cancer" diagnosis in prostate biopsies using a novel "Disease-Focused Diagnostic Review" quality improvement process.

One of the major goals of an anatomic pathology laboratory quality program is to minimize unwarranted diagnostic variability and equivocal reporting. This study evaluated the utility of Miraca Life Sciences' "Disease-Focused Diagnostic Review" (DFDR) quality program in improving interobserver diagnostic reproducibility associated with classification of "atypical glands suspicious for adenocarcinoma" (ATYP) in prostate biopsies. Seventy-one selected prostate biopsies with a focus of ATYP were reviewed by 8 pathologists. Participants were blinded to the original diagnosis and were first asked to classify the ATYP as benign, atypical, or limited adenocarcinoma. DFDR comprised a "theoretical consensus" (in which pathologists first reached consensus on the morphological features they considered relevant for the diagnosis of limited prostatic adenocarcinoma), a didactic review including relevant literature, and "practical consensus" (pathologists performed joint microscopic sessions, reconciling each other's observations and positions evaluating a separate unique slide set). Participants were finally asked to reclassify the original 71 ATYP cases based on knowledge gleaned from DFDR. Pre- and post-DFDR interobserver reproducibility of overall diagnostic agreement was assessed. Interobserver reproducibility measured by Fleiss κ values of pre- and post-DFDR was 0.36 and 0.59, respectively (P=.006). Post-DFDR, there were significant improvement for "100% concordance" (P=.011) and reduction for "no consensus" (P=.0004) categories. Despite a lower pre-DFDR reproducibility for non-uropathology fellowship-trained (n=3, κ=0.38) versus uropathology fellowship-trained (n=5, κ=0.43) pathologists, both groups achieved similarly high post-DFDR κ levels (κ=0.58 and 0.56, respectively). DFDR represents an effective tool to formally achieve diagnostic consensus and reduce variability associated with critical diagnoses in an anatomic pathology practice.

Precursor lesions of mucinous carcinoma of the breast: analysis of 130 cases.

Mucinous mammary carcinoma (MC) is a tumor type with relatively favorable prognosis. Unlike the circumstances surrounding conventional invasive duct carcinoma, data are limited regarding precursor lesions for MC. This study characterizes patterns of mucinous ductal carcinoma in situ (DCIS) as a precursor lesion for MC. All slides from 130 cases of MC encountered between 2000 and 2011 at Henry Ford Hospital, Detroit, MI were reviewed to subclassify MC, identify DCIS, and explore transition patterns from DCIS to MC. Calponin, p63, chromogranin, synaptophysin, CD56, and MIB-1 immunostaining analyses were performed in 65 cases. Among 106 cases of pure (71 type A, 35 type B) and 24 cases of mixed MC, DCIS appeared in 88 (68%) specimens, with all but 4 showing luminal mucin accumulation. Dominant patterns of mucinous DCIS were cribriform/solid (66), cribriform and papillary (7), papillary (5), micropapillary (3), and flat (3). Fifty-seven (68%) cases of mucinous DCIS demonstrated transitions from DCIS to MC. Luminal mucinous distention, focal flattening and attenuation of the epithelium, and disruption of the duct wall resulting in a mucocele-like extravasation of malignant epithelia with escaping mucin was a transition pattern seen with all architectures of DCIS and in all types of MC. This was the only pattern of transition to type A MC. The epithelial outpouching, formation of a cleft with accumulation of mucin around the epithelium, and transition into mucin pools with floating tumor cell clusters was the second transition pattern that went from cribriform/solid DCIS to type B and mixed MC. DCIS preceding aggressive phenotypes of MC (type B and mixed) more often had a cribriform/solid architecture, higher nuclear grade, and higher Ki-67-labeling index (all P<0.05). In summary, mucinous DCIS is a precursor to MC with distinctive features that link patterns of DCIS with aggressive MC phenotypes. The 2 observed transitions between mucinous DCIS and MC suggest that pathogenesis of different types of MC is different correlating with less or more aggressive behavior of the latter.

Mucinous adenocarcinoma of the endometrium: case series and review of the literature.

OBJECTIVE: Mucinous carcinoma of the endometrium (MCE) is a rare histologic type representing less than 5% of all endometrial carcinomas. The aim of the study was to describe our experience with MCE and determine its clinical outcome. METHODS: After institutional review board approval, we performed a comprehensive retrospective review of medical records of patients with uterine adenocarcinoma who underwent surgical staging for MCE in 2 large academic centers between 1990 and 2009. Patients with 2009 International Federation of Gynecology and Obstetrics stages I to III were included. Patients' demographics and tumor characteristics were obtained and analyzed, including data on follow-up and survival. RESULTS: Thirty-one patients with MCE were identified for the study. Median age was 62 years (range, 43-91 years). All patients underwent surgical staging with lymph node evaluation. Patients' distribution by stage was as follows: 83.9% (n = 26) stage IA, 6.5% (n = 2) stage IIIA, and 9.7% (n = 3) stage IIIC1. Median follow-up was 62 months (range, 1-189 months). Only 30 patients received adjuvant platinum-based chemotherapy. No patients received adjuvant radiation treatment after hysterectomy. Only 4 patients had tumor recurrences with a median time to recurrence of 13.5 months (range, 8-30 months). Three patients with stage IIIC1 and one patient with stage IIIA had a diagnosis of pelvic recurrences. On univariate analysis, factors associated with recurrence were advanced stage (P ≤ 0.0001), deep myometrial invasion (P = 0.0199), lower uterine segment involvement (P = 0.0038), and grade II disease (P = 0.0013). Five-year relapse-free survival was 86.3%, and 5-year overall survival was 81.2%. CONCLUSIONS: Based on our study cohort, the outcome of patients with FIGO stage I to stage II MCE is excellent with surgical staging alone. However, patients with advanced stages may potentially benefit from adjuvant therapies. These findings need to be validated with other similar studies.