Orbital immunoglobulin‐G4‐related disease: case series and literature review

Immunoglobulin‐G4‐related disease (IgG4‐RD) is a distinct group of diseases characterized by elevated serum IgG4 titres and infiltration of affected organs by IgG4‐positive plasma cells. IgG4‐RD can involve any ocular adnexal tissue. They have a distinct prognosis and pattern of tissue involvement and hence need to be differentiated from orbital lesions with similar clinicopathological features. We report three cases of IgG4‐RD and review the literature extensively discussing various aspects of this novel entity.     

Sebaceous carcinoma: clinicopathologic features and diagnostic role of immunohistochemistry (including androgen receptor)

Objective

To explicate the clinicopathologic features of periocular sebaceous carcinoma (SC) and emphasize the importance of immunohistochemical staining that includes androgen receptor (AR) in their diagnosis.

Design

Retrospective study.

Methods

Clinical and histopathologic features in 56 patients with periocular SC were analyzed. Immunohistochemical staining for pan-cytokeratin (CK), epithelial membrane antigen (EMA), Ber-EP4, adipophilin (ADP), and AR was performed on all cases. Immunostaining in SC was compared with that of squamous cell carcinoma (SCC; n = 25) and basal cell carcinoma (BCC; n = 18) for all antibodies.

Results

SGC was more frequent in females, most commonly presenting as a discrete and nodular mass. Four patients had regional lymph node metastases, whereas in 2, the tumour metastasized to the liver. Eight patients had a locoregional recurrence between the 3rd and 45th months of follow-up. Fifty patients had a moderately differentiated tumour. In 3 patients, the resected margins displayed intraepithelial tumour spread, and 2 patients died of the disease. In general, the staining pattern in SGC was CK⁺, EMA⁺, BerEP4^–, ADP⁺, and AR⁺. SCCs were CK⁺, EMA⁺, Ber-EP4^–, ADP^–/+, and AR^–, whereas BCC were CK⁺, EMA^–, Ber-EP4⁺, ADP^–, and AR^–/+. p53 expression and Ki-67 index were higher in SC than SCC or BCC.

Conclusions

Immunostaining using a panel of antibodies comprising BerEP4, ADP, EMA, and AR is useful in diagnosing sebaceous carcinoma and differentiating it from SCC and BCC, which are common to the periocular location and sometimes are morphologically identical to SC.     

Periocular sebaceous gland carcinoma: A comprehensive review

Sebaceous gland carcinoma (SGC) is a rare tumour occurring at periocular and extra-ocular sites. SGC can be a challenging diagnosis for both clinicians and pathologists. High recurrence rates and a tendency for intra-epithelial spread, locoregional and distant metastases make it important for SGC to be suspected and be included in the differential diagnosis of an eyelid lesion. Early diagnosis, that may sometimes need ancillary testing, and prompt management using a multimodal approach can help reduce morbidity and mortality in patients with SGC.     

Phosphatase: PP2A structural importance,regulation and its aberrant expression in cancer

Protein Phosphatase 2A (PP2A) is an important and ubiquitously expressed serine threonine phosphatase and regulates the function by dephosphorylating many critical cellular molecules like Akt, p53, c-Myc and β-catenin. It plays a critical role in cellular processes, such as cell proliferation, signal transduction and apoptosis. Structurally, it is multifarious as it is composed of catalytic, scaffold and regulatory subunits. The catalytic and scaffold subunits have two isoforms and the regulatory subunit has four different families containing different isoforms. The regulatory subunit is the most diverse with temporal and spatial specificity. PP2A undergoes post-translational modifications (i.e. phosphorylation and methylation), which in turn, regulates its enzymatic activity. Aberrant expression, mutations and somatic alterations of the PP2A scaffold and regulatory subunits have been observed in various human malignancies, including lung, breast, skin and colon cancer, highlighting its role as a ‘tumor suppressor’. This review is focused on the structural complexity of serine/threonine phosphatase PP2A and summarizes its expression pattern in cancer. Additionally, the PP2A interacting and regulatory proteins and substrates are also discussed. Finally, the mouse models developed to understand the biological role of PP2A subunits in an in vivo model system are also reviewed in this article.     

Glucosylceramide synthase upregulates <Emphasis Type="Italic">MDR1</Emphasis> expression in the regulation of cancer drug resistance through <Emphasis Type="Italic">cSrc</Emphasis> and β-catenin signaling

Background  

Drug resistance is the outcome of multiple-gene interactions in cancer cells under stress of anticancer agents. MDR1 overexpression is most commonly detected in drug-resistant cancers and accompanied with other gene alterations including enhanced glucosylceramide synthase (GCS). MDR1 encodes for P-glycoprotein that extrudes anticancer drugs. Polymorphisms of MDR1 disrupt the effects of P-glycoprotein antagonists and limit the success of drug resistance reversal in clinical trials. GCS converts ceramide to glucosylceramide, reducing the impact of ceramide-induced apoptosis and increasing glycosphingolipid (GSL) synthesis. Understanding the molecular mechanisms underlying MDR1 overexpression and how it interacts with GCS may find effective approaches to reverse drug resistance.     

Secular Increases in Spontaneous Subarachnoid Hemorrhage during Pregnancy: A Nationwide Sample Analysis

Importance: Understanding of the epidemiology, outcomes, and management of spontaneous subarachnoid hemorrhage (sSAH) during pregnancy is limited. Small, single center series suggest a slight increase in morbidity and mortality. Objective: To determine if incidence of sSAH in pregnancy is increasing nationally and also to study the outcomes for this patient population. Design, Setting, and Participants: A retrospective analysis was performed utilizing the Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project for the years 2002-2014 for sSAH hospitalizations. The NIS is a large administrative database designed to produce nationally weighted estimates. Female patients age 15-49 with sSAH were identified using the International Classification of Diseases, 9th Revision, Clinical Modification code 430. Pregnancy and maternal diagnosis were identified using pregnancy related ICD codes validated by previous studies. The Cochran-Armitage trend test and parametric tests were utilized to analyze temporal trends and group comparisons. Main Outcomes and Measures: National trend for incidence of sSAH in pregnancy, age, and race/ethnicity as well as associated risk factors and outcomes. Results: During the time period, there were 73,692 admissions for sSAH in women age 15-49 years, of which 3978 (5.4%) occurred during pregnancy. The proportion of sSAH during pregnancy hospitalizations increased from 4.16 % to 6.33% (P-_Trend < .001) during the 12 years of the study. African-American women (8.19%) and Hispanic (7.11%) had higher rates of sSAH during pregnancy than whites (3.83%). In the NIS data, the incidence of sSAH increased from 5.4/100,000 deliveries (2002) to 8.5/100,000 deliveries (2014; P-_Trend < .0001). The greatest increase in sSAH was noted to be among pregnant African-American women from (13.4 [2002]) to (16.39 [2014]/100,000 births). Mortality was lower in pregnant women (7.69% versus 17.37%, P < .0001). Pregnant women had a higher likelihood of being discharged to home (69.78% versus 53.66%, P < .0001) and lower likelihood of discharge to long term facility (22.4% versus 28.7%, P < .0001) than nonpregnant women after sSAH hospitalization. Conclusions and Relevance: There is an upward trend in the incidence of sSAH occurring during pregnancy. There was disproportionate increase in incidence of sSAH in the African American and younger mothers. Outcomes were better for both pregnant and nonpregnant women treated at teaching hospitals and in pregnant women in general as compared to nonpregnant women.     

Computed Tomography Angiogram Derived From Computed Tomography Perfusion Done with Low Iodine Volume Protocol Preserves Diagnostic Yield for Middle Cerebral Artery-M2 Occlusions

Background: Computed tomography angiogram (CTA) derived from computed tomography perfusion (CTP) has been proposed to avoid addition of separate CT perfusion protocol for selection of large vessel occlusion in acute stroke patients. Previous studies have validated this technique for proximal large vessel occlusions. In this study, we test reliability for identifying M2 occlusions on CTA derived from CTP. Methods: Through a retrospective search of the institutional thrombectomy database, we identified 28 cases with M2-MCA occlusion, of which 24 met the inclusion criteria for analysis. An additional 20 cases without M2-MCA occlusion (either normal or M1-MCA occlusion) were randomly mixed in the database to reduce observer bias. The baseline images of the CTP study in these 48 cases were then independently analyzed by 3 readers with varying level of expertise. The digital subtraction angiography (DSA) images were also independently reviewed where available. The percentage of agreement among reviewers as well as the probability of agreement of the reviewers, when compared to the DSA findings was also calculated. Results: The observed agreement for the image quality amongst the 3 readers (n = 48) varied between 0.78 and 0.95 and tended to be higher for the M1 segment MCA and lower for distal M2-MCA. The observed agreements comparing 3 image reviewers versus DSA in M2 patients (n = 24) was 98% for identifying occlusion (95% CI 95%-100%), 94% for identifying proximal M2 occlusion (95% CI 88%-98%), and 91% (95% CI 84%-97%) and 90% (95% CI 83%-95%), respectively for correctly identifying inferior and superior branch of M2 occlusion. Conclusion: CTA data derived from CT Perfusion study preserves diagnostic yield for correctly identifying M2 occlusion.