Summary Despite the controversies, estrogen receptor–negative/progesterone receptor–positive (ER−/PR+) breast cancers have a reported incidence of 1% to 4%. These tumors are less well defined, and it ...is unclear whether ER−/PR+ represents a distinct subtype. Thus, we analyzed 5374 consecutive breast cancers to characterize the clinicopathological features of this underrecognized subset of tumors. The ER−/PR+ tumors, constituting 2.3% of the total, were mostly high grade and significantly seen in younger patients and African American women when compared with the ER+/PR+ and ER+/PR− groups, but similar to that of ER−/PR− phenotype ( P < .0001). A significantly prolonged relapse-free survival (RFS) was associated with the ER+/PR+ subtype when compared with the ER+/PR− ( P = .0002) or ER−/PR+ ( P = .0004) tumors, whereas all 3 groups showed a superior outcome to that of the ER−/PR− phenotype. In the subset of patients receiving endocrine therapy, those with ER+/PR+ tumors had a significantly prolonged RFS ( P = .001) and disease-specific survival ( P = .005) when compared with the group with an ER+/PR− phenotype, but did not significantly differ from those with ER−/PR+ tumors. No significant survival advantage was found between the ER+/PR− and ER−/PR+ tumors in any group of patients analyzed. Furthermore, a higher PR expression was associated with a favorable RFS and disease-specific survival in the patients with ER−/PR+ tumors. Therefore, the ER−/PR+ tumors demonstrate a similar, if not higher than, response rate to endocrine therapy when compared with the ER+/PR− tumors and thus are important to identify. Routine PR testing remains necessary in assisting clinical decision making in the pursuit of precision medicine.
Summary We report 3 new patients with sinonasal renal cell–like adenocarcinoma (SNRCLA). One case submitted in consultation demonstrated robust carbonic anhydrase IX (CA-IX) expression, leading us to ...a broader inquiry of CA-IX and carbonic anhydrase II (CA-II) expression in other SNRCLA, Schneiderian tissues, and histologic mimickers. Robust cytoplasmic and membranous CA-IX expression is demonstrated in 6 of 7 SNRCLAs; CA-II expression was demonstrated in 2 of 5 cases. Robust, diffuse CA-II expression is demonstrated throughout sinonasal seromucinous glands in all 10 normal Schneiderian samples. CA-IX is also expressed in all normal sinonasal samples, albeit focally. The closest salivary mimic to SNRCLA is hyalinizing salivary clear cell carcinoma; only focal CA-IX expression was demonstrated in 1 of 2 cases studied. Carbonic anhydrase expression in Schneiderian tissue speaks to its role in regulating the ion concentration of sinonasal secretions and may also explain the origin of this rare tumor.
Summary We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans and 72 whites) comparing rates of transcriptionally active human papillomavirus ...(HPV)16/18 and p16INK4a overexpression, with times to disease progression and disease-specific survival (DSS). Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16INK4a was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16INK4a in OPC was significantly more common in African Americans (15/24) than in whites (20/69) ( P = .004) and in HPV16+ African Americans (6/24) than in HPV+ whites (2/42) ( P = .023). Kaplan-Meier analysis for DSS revealed a protective effect for p16INK4a overexpression ( P = .0028; hazard ratio HR, 0.23), HPV16+ ( P = .036; HR, 0.38), and whites ( P = .0039; HR, 0.27). Shorter DSS was associated with primary definitive chemoradiation ( P = .019; HR, 3.49) and T3/T4 disease ( P = .0001; HR, 7.75). A protective effect with respect to disease progression was observed for HPV16+ ( P = .007; HR, 0.27), whites ( P = .0006; HR, 0.197), and p16INK4a overexpression ( P = .0001; HR, 0.116). African Americans with OPC experience poorer outcomes likely due to p16INK4a silencing, higher T stage, and nonsurgical treatment but not lower rates of transcriptionally active HPV16/18.
Frozen section: guiding the hands of surgeons? McIntosh, Eleanor R., MD; Harada, Shuko, MD; Drwiega, Joseph, MD ...
Annals of diagnostic pathology,
10/2015, Letnik:
19, Številka:
5
Journal Article
Recenzirano
Abstract Frozen section (FS) analysis is a powerful tool that can provide a rapid diagnosis, directing operative management. However, FSs can also be misused. We consider an FS to be “inappropriate” ...when it does not influence operative management or immediate patient care. Not only can inappropriate FSs compromise diagnostic material, they can impact turnaround time of other FSs. We evaluated the utilization of FSs at our institution and assessed influence on intraoperative management. Frozen sections performed at the University of Alabama at Birmingham Hospital in 2013 were stratified by surgical subspecialty. Operative, clinical, and pathology notes were reviewed to determine the rationale for sending each FS and to determine impact on intraoperative management. Cases lacking operative notes were excluded. A total of 4104 FSs were performed in 1896 cases. Surgical subspecialties included cardiothoracic, otolaryngology, breast, surgical oncology, gynecology, gastrointestinal, hepatobiliary, urology, transplant, and orthopedics. 42.5% of FSs evaluated margin status, 34.8% confirmed or excluded malignancy, 9.5% were for tumor classification, 6.7% assessed adequacy for diagnosis, 1.9% were to confirm or exclude infection, 2.8% were for transplant, and 1.8% were for lymphoma workup. Twelve percent (491/4104) of FSs did not influence operative management. This was most common among cardiothoracic surgeries (34%). No inappropriate FSs were sent for any transplant surgeries. Otolaryngology used the most FSs and had less than 1% that were inappropriate. Most FSs influence operative management. The rationale for sending an FS and its influence on operative management was subspecialty dependent. Interdepartmental discussions of FS utilization might be helpful in the elimination of unnecessary FSs.
Summary High-throughput gene expression profiling from formalin-fixed, paraffin-embedded tissues has become a reality, and several methods are now commercially available. The Illumina whole-genome ...complementary DNA–mediated annealing, selection, extension and ligation assay (Illumina, Inc) is a full-transcriptome version of the original 512-gene complementary DNA–mediated annealing, selection, extension and ligation assay, allowing high-throughput profiling of 24 526 annotated genes from degraded and formalin-fixed, paraffin-embedded RNA. This assay has the potential to allow identification of novel gene signatures associated with clinical outcome using banked archival pathology specimen resources. We tested the reproducibility of the whole-genome complementary DNA–mediated annealing, selection, extension and ligation assay and its sensitivity for detecting differentially expressed genes in RNA extracted from matched fresh and formalin-fixed, paraffin-embedded cells, after 1 and 13 months of storage, using the human breast cell lines MCF7 and MCF10A. Then, using tumor worst pattern of invasion as a classifier, 1 component of the “risk model,” we selected 12 formalin-fixed, paraffin-embedded oral squamous cell carcinomas for whole-genome complementary DNA–mediated annealing, selection, extension and ligation assay analysis. We profiled 5 tumors with nonaggressive, nondispersed pattern of invasion, and 7 tumors with aggressive dispersed pattern of invasion and satellites scattered at least 1 mm apart. To minimize variability, the formalin-fixed, paraffin-embedded specimens were prepared from snap-frozen tissues, and RNA was obtained within 24 hours of fixation. One hundred four down-regulated genes and 72 up-regulated genes in tumors with aggressive dispersed pattern of invasion were identified. We performed quantitative reverse transcriptase polymerase chain reaction validation of 4 genes using Taqman assays and in situ protein detection of 1 gene by immunohistochemistry. Functional cluster analysis of genes up-regulated in tumors with aggressive pattern of invasion suggests presence of genes involved in cellular cytoarchitecture, some of which already associated with tumor invasion. Identification of these genes provides biologic rationale for our histologic classification, with regard to tumor invasion, and demonstrates that the whole-genome complementary DNA–mediated annealing, selection, extension and ligation assay is a powerful assay for profiling degraded RNA from archived specimens when combined with quantitative reverse transcriptase polymerase chain reaction validation.
Abstract Vocal cords stiffness can be associated with a variety of etiologic agents, but it is rarely seen with atypical mycobacteria, for example, Mycobacterium avium complex. We report a case of a ...35-year-old white woman who is and was maintained on inhaled steroids. She presented with hoarseness and low-grade fever, but her medical history was otherwise unremarkable. Laryngoscopy revealed bilateral scarring of the vocal cords. Vocal cord biopsies were performed. Histologic examination revealed unremarkable laryngeal mucosa, except for abundant subepithelial non-necrotizing granulomata. The differential diagnosis included sarcoid, Klebsiella scleroma, and tuberculosis. Special stains reviewed abundant acid-fast bacilli, later confirmed by a DNA assay on induced deep sputum, consistent with M avium complex. Subsequently, steroids were withdrawn, and the patient was treated with a multiple-drug antituberculous regimen and had a full recovery. This unusual clinical presentation of the atypical mycobacteriosis may be encountered by otolaryngologists and pathologists, and it is critical to recognize it in patients immunocompromised because of steroids.
