Although the majority of low grade, early stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes β-catenin) mutations identify a subset of low grade, early stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the β-catenin protein from the membrane to the nucleus and activation of Wnt/β-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of β-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wildtype tumors. Nuclear localization of β-catenin had 100% specificity in distinguishing CTNNB1 mutant from wildtype, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5–10% of tumor cells with β-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. Extent of β-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of β-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of β-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. Extent of nuclear localization may be tumor-type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of β-catenin is absent.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV MCU) is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. It has not been reported in solid organ transplant recipients. We observed 7 patients with EBV MCU in a cohort of 70 transplant recipients with EBV posttransplant lymphoproliferative disorder (PTLD). Transplants included: 5 renal, 1 heart, and 1 lung. Median patient age was 61; 5 were male. EBV MCU was observed in oral mucosa in 4 and gastrointestinal tract in 3. Duration of immunosuppressive therapy before EBV MCU was 0.6 to 13 years. Ulcers were undermined by inflammatory cells and polymorphic or monomorphic large cell lymphoproliferation. Reed-Sternberg-like cells were present in 5/7. Large B cells were CD20, CD30, and EBV-encoded RNA positive in all cases. Diagnosis in 3 recent patients was EBV MCU; 4 patients diagnosed before familiarity with EBV MCU were classified as monomorphic large cell (n=3) and polymorphic (n=1) PTLD. None of the patients had EBV DNA in their blood (<1000 copies/mL) at diagnosis or follow-up versus 35/44 transplant patients with systemic PTLD (P<0.001). All lesions resolved with reduced immunosuppression (7/7), change in immunosuppression (2/7), and rituximab (3/7). Five patients are living: 4 healthy, 1 awaiting second renal transplant. Two patients died 3 and 5 years after resolution of EBV MCU. No patient recurred with EBV MCU or other PTLDs. EBV MCU mimics more aggressive categories of PTLD but lacks EBV DNA in blood, which may be a useful distinguishing feature. Lesions are likely to resolve with conservative management. Awareness of EBV MCU in the posttransplant setting is necessary for appropriate diagnosis and treatment.

No abstract

T cell activation is controlled by incompletely defined opposing stimulation and suppression signals that together sustain the balance between optimal host defense against infection and peripheral tolerance. Herein, we explored the impacts of Foxp3+ regulatory T cell (Treg) suppression in priming antigen-specific T cell activation under non-infection and infection conditions. We find the transient ablation of Foxp3+ Tregs unleashes the robust expansion and activation of peptide stimulated CD8+ T cells that provide protection against Listeria monocytogenes (Lm) infection in an antigen-specific fashion. By contrast, Treg-ablation had non-significant impacts on the CD8+ T cell response primed by infection with recombinant Lm. Similarly, non-recombinant Lm administered with peptide stimulated the expansion and activation of CD8+ T cells that paralleled the response primed by Treg-ablation. Interestingly, these adjuvant properties of Lm did not require CD8+ T cell stimulation by IL-12 produced in response to infection, but instead were associated with sharp reductions in Foxp3+ Treg suppressive potency. Therefore, Foxp3+ Tregs impose critical barriers that when overcome naturally during infection or artificially with ablation allows the priming of protective antigen-specific CD8+ T cells.

Quantitative real-time polymerase chain reaction is a technique for simultaneous amplification and product quantification of a target DNA as the process takes place in real time in a "closed-tube" system. Although this technique can provide an absolute quantification of the initial template copy number, quantification relative to a control sample or second sequence is typically adequate. The quantification process employs melting curve analysis and/or fluorescent detection systems and can provide amplification and genotyping in a relatively short time. Here we describe the properties and uses of various fluorescent detection systems used for quantification.

Alveolar rhabdomyosarcoma is an uncommon tumor affecting adolescents and young adults that is only rarely encountered in body fluid cytology. We report the cytological features of metastatic alveolar rhabdomyosarcoma in the ascitic fluid of a 17-year-old female patient, who had presented with abdominal distention, 21 months after being diagnosed with perirectal alveolar rhabdomyosarcoma. The rare single neoplastic cells that were admixed with abundant reactive mesothelial cells were initially misinterpreted as reactive mesothelial cells. However, their neoplastic nature was established after a careful review of their cytological features and the performance of immunoperoxidase stains. Compared to the reactive mesothelial cells that were present in the sample, the malignant cells were smaller, with less ample and more homogenous cytoplasm. They had slightly larger, more hyperchromatic, and more frequently eccentric nuclei, with larger nucleoli. This case highlights the potential pitfall of the misinterpretation of metastatic alveolar rhabdomyosarcoma cells for reactive mesothelial cells. Awareness of this potential diagnostic problem and recognition of the cytomorphological features of this neoplasm in the body fluids allows the identification of malignant cells, even when they are rare and intimately associated with mesothelial cells.

The purpose of the study was to describe the normal anatomy of the glenoid labrum to help identification of pathology and guide surgical repair. Twenty dry bone scapulae and 19 cadaveric shoulders were examined. Light microscopy was performed on 12 radial slices through the glenoid. An external capsular circumferential ridge, 7-8 mm medial to the glenoid rim marks the attachment of the capsule. A separate internal labral circumferential ridge 4 mm central to the glenoid rim marks the interface between the labrum and articular cartilage. A superior-posterior facet was found consistently on the glenoid. Two thirds of the long head of biceps arises from the supraglenoid tubercle, 6.6 mm from the glenoid face, the remainder from the labrum. The superior labrum is concave and is loosely attached to the articular cartilage and glenoid rim. Clefts and foramens are common superiorly. In contrast the anterior-inferior labrum is convex, attaches 4 mm central to the glenoid rim and has a strong attachment to articular cartilage and bone. Sublabral clefts, recesses, and holes are common, but only in the superior-anterior labrum. Lesions in other regions of the labrum are potentially pathological. A complex superior labrum tear that extends to involve the biceps anchor, should have the biceps anchor repaired to the supraglenoid tubercle (mean 6.6 mm off the glenoid face) and the labrum be repaired to the glenoid rim. The anteroinferior labrum should be repaired 4 mm onto the glenoid face. This study will aid in identifying pathological labral lesions and guide anatomic repairs.

Epithelioid angiosarcomas (EAS) of kidney are rare and aggressive tumors with noncharacteristic imaging features that overlap with those of inflammatory conditions and renal cell carcinoma (RCC). We report the fine-needle aspiration (FNA) cytology findings of a case of EAS that involved the left kidney of an 83-year-old male. The smears and cell block sections showed pleomorphic epithelioid cells with ample cytoplasm, eccentric nuclei, occasional cytoplasmic hyaline globules, and rare intracytoplasmic lumina. Immunohistochemical stains performed on cellblock sections showed that the tumor cells were positive for vimentin, CD31, CD34, Factor VIII, and CD10, but showed no staining for cytokeratins AE1/AE3 and 8/18, HMB45, CD45, smooth muscle actin, and S100. The morphological and immunohistochemical distinction between EAS, primary tumors of the kidney, and other epithelioid and rhabdoid neoplasms is discussed.