Faculty Bibliography

Erdheim"“Chester disease (ECD) is a rare, non-Langerhans histiocytic disease, with the manifestation of cutaneous lesions becoming further recognised and understood. Most commonly presenting with xanthelasma-like lesions, cutaneous manifestations are the first noticeable sign of ECD in a significant number of patients. Other commonly reported cutaneous lesions of ECD include panniculitis-like lesions and granuloma annulare-like lesions. While previously reported papular lesions of ECD include crusty yellow and erythematous papules, small, pink to fleshy coloured papules, and verruca plana-like papules, papulonodular eruptions consistent with fibrous histiocytomas are a rare and underreported sequala of ECD. Here, we report an 86-year-old male with a history of prostate and bladder cancer who presented with eruptive fibrous histiocytomas, prompting workup that lead to a diagnosis of ECD. The patient received expedited imaging given the rare association of eruptive fibrohistiocytic lesions with malignancy, revealing diffuse perinephric and urothelial soft tissue thickening and enhancement, which was biopsied and found to harbour the BRAF V600E mutation. One could reasonably hypothesise that the pathologic mechanism occurring in the perinephric and urothelial soft tissue areas of this patient bodes similarities to the cutaneous sites consistent with the fibrohistiocytic lesions. This may present a potential clue to the poorly understood origin and pathogenesis of ECD.

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

Mucormycosis, also known as black fungus, is a rare but aggressive fungal disease with high morbidity and mortality rates that tends to affect patients who are severely immunocompromised. Early recognition of the infection and prompt intervention is critical for treatment success. In recent years the COVID-19 pandemic has resulted in a surge in the number of cases of mucormycosis. This study aims to report an unfortunate event involving an immunocompromised elderly male with mucormycosis of the foot who expired from sepsis due to COVID-19. It is important to have a high clinical suspicion for mucormycosis when a clinical lesion develops, and to appropriately biopsy the lesion in question, particularly in a context of COVID-19. Raising awareness of COVID-19-associated mucormycosis may allow for early detection of the disease, thus enabling the initiation of rapid treatment, ultimately saving lives.

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.