Faculty Bibliography

Basal tumor propagating cells (TPCs) control squamous cell carcinoma (SCC) growth by self-renewing and differentiating into supra-basal SCC cells, which lack proliferative potential. While transcription factors such as SOX2 and KLF4 can drive these behaviors, their molecular roles and regulatory interactions with each other have remained elusive. Here, we show that PITX1 is specifically expressed in TPCs, where it co-localizes with SOX2 and TRP63 and determines cell fate in mouse and human SCC. Combining gene targeting with chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic analyses reveals that PITX1 cooperates with SOX2 and TRP63 to sustain an SCC-specific transcriptional feed-forward circuit that maintains TPC-renewal, while inhibiting KLF4 expression and preventing KLF4-dependent differentiation. Conversely, KLF4 represses PITX1, SOX2, and TRP63 expression to prevent TPC expansion. This bi-stable, multi-input network reveals a molecular framework that explains self-renewal, aberrant differentiation, and SCC growth in mice and humans, providing clues for developing differentiation-inducing therapeutic strategies.

Lymphomatoid papulosis is often regarded as a low-grade variant of cutaneous T cell lymphoma (CTCL). Given the excellent long-term prognosis, recent consensus guidelines indicate that patients can be monitored off therapy. We report a case of a 67-year-old man who presented with lymphomatoid papulosis, with necrotic papules that have been intermittently present for over forty years.

The pathophysiology of generalized essential telangiectasia is not well understood. Generalized essential telangiectasia is an uncommon disorder in which widespread telangiectasias of unknown cause develop without associated systemic or antecedent dermatologic disease. We report a case of generalized essential telangiectasia in an otherwise healthy 49-year-old man.

We present a case of necrobiosis lipoidica (NL) of the right abdomen in a 75-year-old man. A skin biopsy performed showed a layered infiltrate of mono and multinucleated histiocytes palisaded around degenerated collagen bundles. Laboratory workup was unremarkable. The patient was treated with topical corticosteroids with cessation of progression of his disease, although the eruption did not resolve. There are a number of treatments for NL reported in the literature, all with varying efficacy. Although NL lesions are usually asymptomatic, patients with NL must be monitored closely for signs of ulceration or malignant transformation, in which case more aggressive treatment options may be warranted.

Folliculotropic mycosis fungoides (MF) is a distinct subset of cutaneous T cell lymphoma (CTCL). The disease is typically marked by an aggressive course and is often recalcitrant to skin-direct therapy. We report a case of an 83-year-old woman with folliculotropic MF characterized by erythematous, scaly plaques on the forehead along with poliosis and alopecia of the right medial eyebrow.

Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus of unclear etiology that predominantly affects patients of skin types III to VI. We report a case of LPP of two years duration in a 67-year-old man involving upper extremities, chest, abdomen, and upper back.

BACKGROUND:Malignant angiomyolipoma is an uncommon tumor of the class of perivasciular epithelioid cell neoplasms (PEComas). These tumors are characteristically driven by deleterious mutations in the tumor suppressors TSC1 and TSC2, whose gene products typically act to inhibit mTOR. There are several cases of malignant angiomyolipoma which exhibit transient responses to mTOR inhibitors, forming the basis of current practice guidelines in malignant PEComa. However the tumors ultimately acquire resistance, and there is no well-established second-line option. Despite the increasing prevalence of immunotherapy across a wide range of solid tumors, little is known about the immune infiltrate and PD-L1 expression of angiomyolipoma. Furthermore, there is no reported case on the treatment of malignant angiomyolipoma with an immune checkpoint inhibitor. CASE PRESENTATION/METHODS:A 38 year-old man presented with gross hematuria and was diagnosed with renal epithelioid angiomyolipoma. Despite surgical resection, the tumor recurred and metastasized. Targeted genomic sequencing revealed a deleterious mutation in TSC2, and the patient was treated with the mTOR inihbitor everolimus. The patient went on to have a partial response but ultimately progressed. He was then treated with the anti-PD-1 immune checkpoint inhibitor nivolumab, and achieved a durable near-complete response which is ongoing after two years of treatment. Immunohistochemical staining of tumor tissue revealed strong PD-L1 expression and a brisk T-cell infiltrate. CONCLUSIONS:We report on the first durable systemic treatment of malignant epithelioid angiomyolipoima with the use of PD-1 antibody nivolumab. Given the absence of prospective clinical trials in this exceedingly rare disease, particularly in the second-line setting, immune checkpoint inhibitors like nivolumab should be considered.