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Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is not required for pulmonary infection establishment, loss of CCR inhibits fungal metabolic plasticity and the ability to thrive in the dynamic infection microenvironment. Our results suggest a model whereby CCR in an environmental filamentous fungus is dispensable for initiation of pulmonary infection but essential for infection maintenance and disease progression. Conceptually, we argue these data provide a foundation for additional studies on fungal factors required to support fungal fitness and disease progression and term such genes and factors, DPFs (disease progression factors).

The medical education literature has presented many experiential teaching paradigms to help faculty teach more effectively in busy clinical settings. Three prominent teaching models are The Aunt Minnie model, the SNAPPS model, and the One-Minute Preceptor. Teaching paradigms can help faculty to develop into effective teachers. Each of these models can be adapted to a busy academic pathology practice. The Aunt Minnie model is effective in cases with high pattern recognition, such as repetitive trays of biopsies. The SNAPPS model is learner directed and is easily adapted for an advanced learner with complex cases requiring ancillary testing. The One-Minute Preceptor method is effective for teachers with groups of learners, such as multiheaded scope sessions.

Our program in is a 4-year combined anatomic pathology (AP) and clinical pathology (CP) program located in New Hampshire. Prior to the novel coronavirus (COVID-19) pandemic, double-headed sign-outs and multi-headed scope didactic conferences took place daily. On the autopsy service, cases were performed in-house under attending supervision, and forensic cases were performed at the off-site Office of the Medical Examiner. In CP, residents engaged in weekly didactic CP lectures and engaged in in-person resident-attending discussions, laboratory rounds, and direct patient contact on a daily basis. Institutional Universal Guidelines from the Emergency Order from New Hampshire were imposed at the beginning of the pandemic. These included exposure mitigation and employee screening strategies. Changes to resident rotations and didactic sessions, strategies to maintain resident wellness, and the program director perspectives are described. Amid the pandemic, digital pathology, teleconferencing platforms, and social media became important resources for pathology education. Digital platforms allowed groups of people to communicate and watch live presentations while social distancing. In AP, whole slide imaging allowed both attendings and residents to scan slides for personal learning, slide conferences, and didactic learning sessions. Following these measures, we supported the clinical needs of our medical center and learning needs of our residents while enacting social distancing and prevention guidelines early in the pandemic. Although the full impact of COVID-19 on pathology residency programs is still unknown, we incorporated new facets of communication technologies. These were immensely helpful in maintaining social distancing and helping to reduce the spread of disease.

Dilated cardiomyopathy (DCM) is often hereditary, with 20% to 40% of nonischemic cases showing familial linkage, yet genetic testing is underused. This report describes an unreported pathogenic nonsense variant in the Titin (TTN) gene (NM_001267550.2:c.92603G>A) in a 24-year-old man with severe DCM and acute fibrinoid organizing pneumonia, highlighting a unique cardiopulmonary pathology. We conducted detailed gross, histopathologic, immunophenotypic, and exome-based DNA sequencing analysis in the workup of this case. We also included the patient's clinical and radiologic findings in our study. With rapid clinical deterioration and complex comorbidities, including substance abuse and psychiatric conditions, which precluded transplantation, the patient's cardiac function progressively worsened. Autopsy findings included extreme cardiomegaly, biventricular hypertrophy, and acute and chronic pericarditis. Significant pulmonary pathology consistent with acute fibrinoid organizing pneumonia was also noted. Molecular testing confirmed a deleterious maternally inherited TTN variant that was absent in the sibling of the proband and the extant medical literature, highlighting its rarity and significance. This case contributes to the ongoing body of work on the impact of TTN variants on DCM. It suggests a potential link between genetic variants and complex cardiac injury patterns, emphasizing the need for further investigation into the interplay between cardiomyopathy and pulmonary pathology.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1

Pathology-related advocacy is best when performed directly by pathologists. Practicing advocacy is included in the Milestones 2.0 and should be introduced during residency training. To understand advocacy education in residency training we surveyed pathologists to ask what training they had in residency, what resources were available, and what experiences were most impressionable. Two types of inquiry were performed. First, a survey to program graduates asking about leadership and advocacy activities during training and about leadership and advocacy activities since graduation. Secondly, focused email and telephone inquiries were made to 12 pathologists-4 in practice for more than 20 years, 4 within the first 10 years of practice, and to 4 PGY4 (postgraduate year 4) residents-asking what training and experiences were available to them, and how they became motivated to become active in practice. Our results showed that resources available outside of the home program have changed through the years and more national resident groups are available that were not available in the past. These groups may educate trainees in leadership and advocacy. Internally, opportunities to shadow faculty at interdepartmental leadership meetings, as well as selection of the chief resident, are enduring tools for honing these skills. Teaching advocacy in training is important and part of the Accreditation Council for Graduate Medical Education core requirements as well as a level 5 Milestone. Education may require a balance of internal and external resources since different programs may offer different opportunities. Shadowing during real advocacy events was the most impressionable experience.

Annual resident recruitment is a complex undertaking that requires many departmental resources of faculty time and effort and in many cases financial investment for meals and lodging. The applicants represent the future of the profession as well as the providers of patient care in the respective training programs. Although we understand the importance of this process, as we become more and more distracted by financial, administrative, and academic duties, the demands of recruitment have not decreased and continue annually. In an attempt to find the best practices for the improvement in our methods of recruitment, a review of the literature on the employment interviews with a specific eye to pathology residency relevant information was conducted. This article reviews some of the factors proven to be important to the applicants as well as an examination of the structure of the interview and the postinterview applicant evaluation process.

Tracheobronchial inflammation and stenosis is an under-recognised and potentially life-threatening complication of granulomatosis with polyangiitis (GPA). Rituximab (RTX), in combination with glucocorticosteroids, is a well-established and effective alternative to cyclophosphamide (CYC) for inducing remission in GPA. However, treatment options remain unclear in cases where patients fail to respond to RTX. Furthermore, a standardised treatment approach to patients with GPA tracheobronchial disease (TBD) remains elusive, especially since the condition is rare and non-invasive identification and monitoring of TBD activity is often inadequate. We report the case of an ANCA-positive GPA patient with widespread ENT and pulmonary involvement initially responsive to high-dose corticosteroids and RTX, whose disease then quickly broke through with aggressive TBD. She was subsequently induced successfully with CYC but attempts to transition to another maintenance immunosuppressive agent failed, despite the addition of avacopan. Ultimately, the quiescence of her TBD was successfully maintained on abatacept and avacopan. Repeated bronchoscopies were instrumental in monitoring her disease and its response to various treatments but also in minimising damage and keeping at-risk airways open. We review the literature on treatment approaches to GPA TBD. In patients with severe, refractory GPA TBD, abatacept should be considered as a therapeutic option.

Background Wire-localized excision of nonpalpable breast cancer is imprecise, resulting in positive margins 25–30% of the time. Methods Patients underwent preoperative supine magnetic resonance imaging (MRI). A radiologist outlined the tumor edges on consecutive images, creating a three-dimensional (3D) view of its location. Using 3D printing, a bra-like plastic form (the Breast Cancer Locator [BCL]) was fabricated, with features that allowed a surgeon to (1) mark the edges of the tumor on the breast surface; (2) inject blue dye into the breast 1 cm from the tumor edges; and (3) place a wire in the tumor at the time of surgery. Results Nineteen patients with palpable cancers underwent partial mastectomy after placement of surgical cues using patient-specific BCLs. The cues were in place in <5 min and no adverse events occurred. The BCL accurately localized 18/19 cancers. In the 18 accurately localized cases, all 68 blue-dye injections were outside of the tumor edges. Median distance from the blue-dye center to the pathologic tumor edge was 1.4 cm, while distance from the blue dye to the tumor edge was <5 mm in 4% of injections, 0.5–2.0 cm in 72% of injections, and >2 cm in 24% of injections. Median distance from the tumor center to the BCL-localized wire and to the clip placed at the time of diagnosis was similar (0.49 vs. 0.73 cm) on specimen mammograms. Conclusions Information on breast cancer location and shape derived from a supine MRI can be transferred safely and accurately to patients in the operating room using a 3D-printed form.