Search

Context.—: Clinical, dermoscopic, and histologic diagnostic criteria may overlap in cases with scarring and nonscarring alopecia, making diagnosis difficult for clinicians and pathologists. New histopathologic discoveries indicate that the cutaneous adnexal structural and homeostatic unit made up of the pilosebaceous unit, eccrine sweat gland coils (ESGCs), and dermal white adipose tissue may have a role in hair follicle renewal., Objective.—: To verify the presence of adipose tissue in the dermis at the level of the isthmus, infiltrating the bundles of the arrector pili muscle in biopsies from the scalp of 3 scarring alopecias: frontal fibrosing alopecia (FFA), fibrosing alopecia in a pattern distribution (FAPD), and lichen planopilaris (LPP)., Design.—: We performed a retrospective and descriptive survey of 71 female scalp biopsies from 2016 to 2022 diagnosed at the Dermatopathology Laboratory at Fluminense Federal University of Rio de Janeiro. Two pathologists reviewed and diagnosed the cases, correlating pathologic features with clinical and dermoscopic findings., Results.—: The histopathologic findings of adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle and the displacement of ESGCs were more frequently identified in FFA, followed by FAPD and less frequently found in LPP., Conclusions.—: According to our research, adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle and the displacement of ESGCs were observed in 3 scarring alopecias (FFA, FAPD, and LPP) and seems to be involved in the development of scarring alopecia., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Red blood cell (RBC) transfusion exposes recipients to hundreds of unmatched minor RBC antigens. This exposure can lead to production of alloantibodies that promote clinically significant hemolytic events. Multiple studies have reported an increased frequency of RBC alloimmunization in patients with autoimmunity. However, cellular and molecular mechanisms that underlie autoimmunity-induced alloimmunization have not been reported. Patients with systemic lupus erythematosus (SLE) have a high frequency of alloimmunization and express a type 1 interferon (IFNα/β) gene signature. Thus, we utilized the pristane-induced lupus mouse model to test the hypothesis that inflammation in lupus promotes RBC alloimmunization, and to examine the potential role of IFNα/β. Intraperitoneal injection of pristane, a hydrocarbon oil, led to autoantibody production, glomerulonephritis, and pulmonary hemorrhage in wild type (WT) mice. Pristane treatment significantly induced serum IFNα and expression of multiple interferon-stimulated genes (ISGs) in peripheral blood and peritoneal fluid cells, including inflammatory macrophages. Following transfusion with allogeneic RBCs expressing the KEL glycoprotein, pristane-treated WT mice produced significantly elevated levels of anti-KEL IgM and anti-KEL IgG, compared to untreated mice. Pristane induced comparable levels of inflammatory cells and cytokines in mice lacking the IFNα/β receptor (IFNAR1 -/- ) or the IFNα/β-inducing transcriptions factors (IRF3/7 -/- ), compared to WT mice. However, pristane-treated IFNAR1 -/- and IRF3/7 -/- mice failed to produce ISGs and produced significantly lower levels of transfusion-induced anti-KEL IgG, compared to WT mice. Thus, pristane induction of a lupus-like phenotype promoted alloimmunization to the KEL RBC antigen in an IFNα/β-dependent manner. To our knowledge, this is the first examination of molecular mechanisms contributing to RBC alloimmunization in a model of autoimmunity. These results warrant further investigation of the role of IFNα/β in alloimmunization to other RBC antigens and the contribution of the IFNα/β gene signature to the elevated frequency of alloimmunization in patients with SLE., (Copyright © 2020 Lee, Madany, El Kadi, Pandya, Ng, Yamashita, Jefferies and Gibb.)

: Almost all patients with EGFR-driven lung cancer who are treated with EGFR tyrosine kinase inhibitors (TKI) develop resistance to treatment. A single base (c.2369C>T) transition mutation, EGFR T790M, is the most frequent resistance event after first-generation exposure to EGFR TKIs. Whether T790M mutation is acquired or is selected from a preexisting clone has been a matter of significant debate. In this study, we show that treatment with EGFR TKIs leads to activation of the NFκB pathway, which in turn induces expression of activation-induced cytidine deaminase (AICDA). In turn, AICDA causes deamination of 5-methylcytosine to thymine at position c.2369 to generate the T790M mutation. Pharmacologic inhibition of the NFκB pathway or knockout of AICDA decreased the frequency or prevented the development of T790M mutation, respectively. In addition, patients treated with first-line EGFR TKI displayed increased expression of AICDA and detection of the T790M mutation upon progression. These results identify the mechanism of T790M acquisition and present an opportunity to target the process to delay or prevent it. SIGNIFICANCE: These findings identify the mechanism behind acquisition of a common resistance mutation to TKI treatment in lung cancer., (©2018 American Association for Cancer Research.)

It is difficult to find lungs of appropriate size for double-lung transplantation in teenagers and small adults. Nevertheless, many young patients suffering from cystic fibrosis are waiting for lung transplantation. We have performed two bilateral lobar transplantations (left lower lobe plus right middle and lower lobe) with good recovery. Details of the technique are described.

Bilateral single lung transplantation (BSLT) (the procedure of choice for double lung replacement) and single lung transplantation (SLT) have at present a low incidence of anastomotic problems. In our experience, we have recorded no death related to anastomotic problems and 4 complications occurred for 33 anastomoses with a follow up of at least 2 months. A stent was temporarily inserted for two patients. The decrease of anastomotic complications is confirmed in the literature. It is one of the reasons why the number of SLT and BSLT performed all over the world increases rapidily to the detriment of heart lung transplantation.

Since 1975 200 tracheal sleeve resections for iatrogenic tracheal and subglottic laryngeal stenoses have been performed in our institution. Preoperative Nd:YAG laser is of paramount help in opening the stenoses. Tracheography is usually performed to specify the length of the stenosis and the distance from the vocal cords. Operative procedures are described. One hundred seventy five (87.5%) patients are definitely cured, but in this group 16 patients required a Montgomery tube for 6 months to 1 year to recover a normal tracheal diameter. Two patients needed a second tracheal sleeve resection. Nine (4.5%) patients died, and 16 (8%) had recurrent stenoses. Stenoses in these patients were treated with use of a tracheostomy tube, a permanent Montgomery tube, or an endotracheal stent. Partial anterior cricoid resections performed in 21 patients have had the same results as those of the whole series. Twenty one laryngeal releases were performed and proved to be efficient and safe. In our experience complications can be avoided by good selection and preparation of the patients, accurate identification of the level and length of the stenosis, and meticulous technique.

For double lung transplantation, lung volume matching is easier comparing the predicted total lung capacities of the donor and recipient and the recipient's true TLC. The major concern in the inability to close the chest when the donor lungs are too large. The technique reported of left lower lobe implantation during bilateral single lung transplantation might be of great value in patients with small lung volume.

Thirteen single lung transplantations have been performed in our department for non-infected end-stage lung diseases. Two patients died after surgery; a female patient died of uterine carcinoma one year and six months after the operation. The remaining ten patients are alive; they have resumed an active life and often working. The number of single lung transplantation is rapidly growing in the world, whereas heart-lung transplantation is regressing considerably.

Between November 1989 and April 1991, 14 bilateral single lung transplantations (BSLT) were performed at our institution using the technique we have described without omentoplasty and rarely cardiopulmonary bypass. The indications included emphysema (8), cystic fibrosis (3), infected fibrosis (1), alveolar microlithiasis (1) and lymphocytic interstitial pneumonitis (1). Maximum mean pulmonary artery pressure was 53 mmHg and minimal right ventricular ejection fraction was 15%. Two patients experienced bronchial complications: 1 complete left bronchial dehiscence, 1 late partial stenosis which required a temporary insertion of a stent. One patient had a posterior dehiscence which healed spontaneously. Five patients died postoperatively (3 of infection, 1 after a volume mismatch and 1 after a circulating anticoagulant). BSLT is the technique of choice for double lung transplantation in adults and heart lung transplantation has very few indications in infected end-stage pulmonary disease. We hope that modification of our immunosuppressive regimen will decrease postoperative mortality.

We present 10 cases of a new double lung transplantation technique: following, then the other, without requiring cardiopulmonary bypass. This "bilateral single" lung transplantation procures all the advantages of single lung transplantation.

The technique of enbloc double lung transplantation described by the Toronto team, with cardiopulmonary bypass, cardioplegia, and tracheal suture is complicated by problems of tracheal anastomosis for its authors. Single lung transplantation has a more straight forward postoperative course and bronchial complications are moderate. We present a new technique of lung transplantation, the "bilateral single lung transplantation". It consists, via a single anterior horizontal incision, of successively performing two single lung transplantations without bypass. This operation has been performed ten times since November 1989. As expected, bronchial healing has been excellent.