Resident Case Tracker.

CONTEXT.­: Acquiring objective, timely, and comprehensive feedback on resident diagnostic performance is notoriously difficult. OBJECTIVE.­: To implement a custom software application (Resident Case Tracker) to improve evaluative diagnostic analysis for residency programs. DESIGN.­: Residents and faculty use a graphical user interface with restricted access to their own cases and evaluations. For each sign-out, residents enter their diagnoses and comments for each case. Faculty are provided a sign-out queue to review the resident diagnosis and select their level of agreement alongside optional comments. After sign-out, residents can review the agreement level and comments for each case, overall sign-out statistics, and organ-specific performance, and they have the option of opening and reviewing groups of cases by agreement status. A sign-out evaluation is automatically generated and stored alongside additional reports. Administrative access allows privileged users to readily review data analytics at both an individual and residency-wide global level. RESULTS.­: A marked increase in completed evaluations and feedback was noted in the initial 36 months of implementation. During a 3-year academic period, faculty completed individual feedback on 33 685 cases and 1073 overall sign-out evaluations. CONCLUSIONS.­: Resident Case Tracker is an invaluable tool for our residency program and has provided unparalleled feedback and data analytics. Throughout residency, trainees have access to each completed sign-out, with the ability to learn from discrepant cases while also monitoring improvements in diagnostic acumen over time. Faculty are able to assess resident milestones much more effectively while more readily identifying residents who would benefit from targeted study.

Surgical Pathology "Boot Camp": A Military Experience.

CONTEXT.­: A common concern in pathology residency training is the variability with which incoming trainees have attained basic pathology competencies during undergraduate medical education. While multifactorial deficiencies are likely due to recent de-emphasis of dedicated pathology courses during preclinical training, accelerating the transition from medical student to pathology resident is critical-particularly in military practice where a greater degree of autonomy is required of recent graduates. OBJECTIVE.­: To describe the implementation and results of a 4-week surgical pathology "boot camp" in the largest military pathology residency program in the United States. DESIGN.­: Interns were administered an assessment on basic pathology knowledge, slide practicals, and a skills self-assessment. All specimens were grossed by interns with constant direct supervision. A daily microscopic didactic session was given by an upper level resident and a daily gross conference was led by the interns. Subsequent academic performance was evaluated via monthly slide practicals and diagnostic agreement with faculty. RESULTS.­: Following boot camp, average scores on the knowledge assessment increased from 36.0% ± 16.2% (standard deviation [SD]) to 80.0% ± 12.6% (SD) (P < .001). Slide practical scores showed an increase from 32% ± 12.0% (SD) to 74.0% ± 16.2% (SD) (P < .001). Skills self-assessment showed a global increase across all measures. Throughout the following academic year, postgraduate year 1 (PGY1) residents performed at the same level of current PGY2 residents, based on surgical pathology faculty diagnostic agreement and slide practical performance. CONCLUSIONS.­: An intense 4-week surgical pathology rotation specifically tailored to incoming interns was successful in transitioning medical students to pathology residents within a relatively short time.

Adenomyoma With Pseudoinvasive Growth Pattern and Serosal Penetration Mimicking Endometrial Carcinoma.

We present a novel case of a 48-yr-old female with a uterine adenomyoma with an unusual pseudoinvasive growth pattern displaying full-thickness penetration beyond the serosal surface in association with a dehisced Caesarian scar. Before hysterectomy, magnetic resonance imaging findings showed an infiltrative lesion suggestive of endometrial carcinoma. An endometrial biopsy was benign but definitive operative management was pursued given the concerning imaging. Gross examination of the uterus demonstrated a 7.2 cm, relatively well-circumscribed polypoid neoplasm with pushing borders extending through the full thickness of the myometrium. A serosal defect with protruding red tissue was noted where the neoplasm penetrated the exterior surface of the uterus. Histologic examination demonstrated benign endometrial glands, associated endometrial stroma, thick-walled vessels, and a prominent smooth muscle component consistent with an adenomyoma. To our knowledge, this unique presentation of a pseudoinvasive adenomyoma extending beyond the serosa is extremely rare and is the first time reported in the literature.

Smooth muscle and adenoma-like renal tumor: a previously unreported variant of mixed epithelial stromal tumor or a distinctive renal neoplasm?

We describe 6 cases of a biphasic renal neoplasm, which we designate smooth muscle and adenoma-like renal tumor, which do not cleanly fit any category as currently defined. There were 4 females and 2 males (age, 27-70 years); neither male had a history of hormone exposure. All 5 neoplasms with available history were discovered incidentally on imaging studies with sizes ranging from 4 to 20 cm. The stroma was composed of smooth muscle fascicles alternating with looser, edematous areas; none of the cases contained ovarian-like stroma. The complex but cytologically benign epithelial component consisted of tubulopapillary nodules, branching tubules, clefts, and large cysts. The stroma of all of the cases labeled diffusely for desmin. Estrogen receptor labeling was absent in 4 cases with only minimal (<10%) weak labeling in the remaining 2. The epithelial component of each case labeled diffusely for cytokeratin 7 and was patchy for α-methyl-CoA racemase (P504S). Carbonic anhydrase IX, HMB45, WT-1, and inhibin were negative. None of the 5 cases tested demonstrated trisomies of chromosome 7 or 17 by fluorescence in situ hybridization. Two patients with significant follow-up are disease free at 18.5 and 2.5 years. Smooth muscle and adenoma-like renal tumor could potentially represent a variant of mixed epithelial stromal tumor, which would expand its reported spectrum. However, the absence of clinical history of hormone exposure, predominance of smooth muscle with lack of ovarian-like stroma, prominence of epithelial nodules, and typical absence of estrogen receptor labeling suggest that it may represent a distinct entity.

VCL-ALK renal cell carcinoma in children with sickle-cell trait: the eighth sickle-cell nephropathy?

We report the third case of a renal cell carcinoma bearing a fusion of the vinculin (VCL) and anaplastic lymphoma kinase (ALK) genes. Like the 2 other reported cases, this neoplasm occurred in a young patient (6 y old) with sickle-cell trait and demonstrated distinctive morphologic features including medullary epicenter, discohesive polygonal or spindle-shaped cells with prominent cytoplasmic vacuoles, and prominent lymphocytic infiltrate. The neoplastic cells demonstrated focal membranous labeling for ALK protein by immunohistochemistry, ALK gene rearrangement by fluorescence in situ hybridization, and a specific VCL-ALK gene fusion by reverse transcriptase polymerase chain reaction. VCL-ALK renal cell carcinoma may represent the eighth sickle-cell nephropathy.

t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases.

Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cathepsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that metastasize.

Primary biliary tract melanoma: Report of a case and review of the literature.

INTRODUCTION: Primary melanoma of the bile duct is extremely rare with only nine cases of primary melanoma of the bile duct reported in the literature. PRESENTATION OF CASE: A 55-year-old previously healthy gentleman developed increasing jaundice over several months and subsequently underwent an ERCP with stone extraction. Cytology brushings in an area of a distal stricture in the bile duct were concerning for cholangiocarcinoma. The patient was referred to our institution and underwent a pancreaticoduodenectomy. The surgical specimen showed a single 4.5cm polypoid lesion located in the bile duct. A diagnosis of melanoma was rendered after immunohistochemical studies on the tumor demonstrated positivity for melanoma markers. Follow-up of the patient with skin, ocular, and lymph node exams showed no evidence of melanoma. A PET scan 4 and 10 months post-surgery failed to reveal either a primary skin lesion or other sites of metastases. DISCUSSION: The vast majority of melanomas of the bile duct represent metastases from a cutaneous source and tend to present as multiple flat pigmented lesions. Conversely, cases of primary bile duct melanoma are characterized by a distinct gross morphology consisting of a solitary intraluminal polypoid lesion attached by a pedicle with no other identifiable primary lesion. Other supporting criteria include absence of other involved sites and presence of an in situ junctional component. CONCLUSION: Given the clinical history, gross findings, and lack of a primary cutaneous site or other demonstrable metastases, this patient likely represents the tenth reported case of primary biliary tract melanoma.

Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

BACKGROUND: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE: We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.