Faculty Bibliography

Many state-wide, city-wide, and hospital-wide changes have been implemented due to the ongoing COVID-19 crisis. We describe lessons learned in an anatomic pathology division at a tertiary care center during the peak of the COVID-19 pandemic in the hopes that knowledge of our experiences can benefit other pathology departments as they encounter this pandemic. Five categories that are critical in strategic planning for the COVID-19 pandemic are discussed: workload, departmental policy revisions, impact on faculty, workforce staffing, and impact on educational programs, including residency and fellowship training. Although the volume of COVID-19 testing had grown placing increased demands on the clinical pathology laboratory, the volume of anatomic pathology cases had declined during the COVID-19 peak. Lessons learned were widespread including changes in the anatomic pathology workflow due to declining surgical and cytologic case volumes and increases in autopsy requests. Modifications were required in gross room policies, levels of personal protective equipment, and workforce. Travel and meeting policies were impacted. Adaptations to residency and fellowship programs were vast and included innovations in didactic and interactive education. We must learn from our experiences thus far in order to move forward, and we hope that our experiences in an anatomic pathology department in the epicenter of the COVID-19 pandemic can help other pathology departments across the country.

Inflammatory orbital lesions include a broad list of diagnoses, many of them with overlapping clinical and radiographic features. They often present a diagnostic conundrum, even to the most experienced orbital specialist, thus placing considerable weight on surgical biopsy and histopathological analysis. However, histopathological diagnosis is also inherently challenging due to the rarity of these lesions and the overlaps in histologic appearance among distinct disease entities. We herein present the case of an adolescent male with a subacutely progressive orbital mass that generated a significant diagnostic dilemma. Early orbital biopsy was consistent with a benign fibro-inflammatory lesion, but corticosteroid therapy was ineffective in halting disease progression. After an initial substantial surgical debulking, histopathological analysis revealed several key features consistent with IgG4-related disease (IgG4-RD), a systemic fibro-inflammatory process typically accompanied by multifocal tumor-like lesions. Surprisingly, within months, there was clear evidence of clinical and radiographic disease progression despite second-line rituximab treatment, prompting a second surgical debulking. This final specimen displayed distinctive features of Rosai-Dorfman disease (RDD), a systemic inflammatory disease characterized by uncontrolled histiocytic proliferation. Interestingly, certain features of this re-excision specimen were still reminiscent of IgG4-RD, which not only reflects the difficulty in differentiating RDD from IgG4-RD in select cases, but also illustrates that these diagnoses may exist along a spectrum that likely reflects a common underlying pathogenetic mechanism. This case emphasizes the importance of surgical biopsy or resection and histopathological analysis in diagnosing-and, ultimately, treating-rare, systemic inflammatory diseases involving the orbit, and, furthermore, highlights the shared histopathological features between RDD and IgG4-RD.

Favorable histology (FH) Wilms tumor (WT) is one of the most curable of all human cancers, yet a small minority of patients fail treatment. The underlying biological pathways that lead to therapy resistance are unknown. We report a case of initially unresectable, FH WT which revealed limited necrosis and persistent blastemal predominant histology following neoadjuvant chemotherapy. Despite intensification of therapy and whole abdominal radiation, the patient relapsed and succumbed to her disease. In an effort to discover candidate drivers of drug resistance, whole exome sequencing and copy number analysis were performed on samples from all 3 tumor specimens. Sequencing results revealed outgrowth of clones with a dramatically different genetic landscape including dominant mutations that could explain therapy evasion, some of which have not been previously reported in WT. Our results implicate PPM1D, previously shown to be associated with drug resistance in other tumors, as the major driver of treatment failure.