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Cutaneous T-cell lymphomas (CTCLs) are a spectrum of diseases with varied clinical courses caused by malignant clonal proliferation of skin-tropic T cells. Most patients have an indolent disease course managed with skin-directed therapies. In contrast, others, especially in advanced stages of disease or with specific forms, have aggressive progression and poor median survival. Sézary syndrome (SS), a leukemic variant of CTCL, lacks highly consistent phenotypic and genetic markers that may be leveraged to prevent the delay in diagnosis experienced by most patients with CTCL and could be useful for optimal treatment selection. Using single-cell mRNA and T-cell receptor sequencing of peripheral blood immune cells in SS, we extensively mapped the transcriptomic variations of nearly 50 000 T cells of both malignant and nonmalignant origins. We identified potential diverging SS cell populations, including quiescent and proliferative populations shared across multiple patients. In particular, the expression of AIRE was the most highly upregulated gene in our analysis, and AIRE protein expression could be observed over a variety of CTCLs. Furthermore, within a single patient, we were able to characterize differences in cell populations by comparing malignant T cells over the course of treatment with histone deacetylase inhibition and photopheresis. New cellular clusters after progression of the therapy notably exhibited increased expression of the transcriptional factor FOXP3, a master regulator of regulatory T-cell function, raising the potential implication of an evolving mechanism of immune evasion.

Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC.The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC.This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used.Sixty-eight subjects (34 metastatic34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p.001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p.001).Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Necrobiosis lipoidica (NL) is an uncommon granulomatous dermatosis that can occur in patients with or without associated diabetes mellitus (DM). Prior studies have attempted to determine distinctive histopathologic features of NL in patients with and without DM.A retrospective review of 97 patients with NL was performed to determine the similar and distinctive histopathologic features in patients with DM and without DM.Of the 97 patients, 32% (n = 31) had DM. Epidermal acanthosis was seen more commonly in diabetics than nondiabetics (32.3% vs. 12.1%; p = 0.017). Naked (sarcoidal/tuberculoid) granulomas were more frequently observed in nondiabetics than diabetics (22.7% vs. 3.2%; p = 0.016). Eosinophils were more common in nondiabetics than diabetics (38.5% vs. 9.7%; p = 0.004), while neutrophilic infiltration was more common in diabetics than nondiabetics (45.2% vs. 17.5%; p = 0.004).This study corroborates well-documented histopathologic features of NL and shows distinctive histopathologic features of NL among patients with DM-I, DM-II, and without DM. These results support the hypothesis that there are different underlying drivers of NL between diabetics and nondiabetics.

Recent advances in chimeric antigen receptor (CAR) T-cell therapy have demonstrated promising results for diseases ranging from acute lymphoblastic leukemia (ALL) to glioblastoma.1,2 Leukemia cutis is a rare manifestation of leukemia, in which leukemic cells infiltrate the skin; as such, there is a paucity of literature describing the effects of CAR T-cell therapy in the context of leukemia cutis. Here we present a case of B-cell lymphoblastic leukemia cutis flaring and spontaneously resolving following CAR T-cell therapy.

We report a case of a 13-year-old boy with extensive lymphomatoid papulosis (LyP) involving his elbows, forearms, proximal thighs, and right hip, with treatment-resistant nodules on his right forearm. He was treated with full-body narrowband ultraviolet B and targeted photodynamic therapy (PDT) with 20% aminolevulinic acid (ALA). After two months, there was complete resolution of the right forearm nodules. Due to its minimal toxicity, PDT offers unique advantages and may be considered for pediatric LyP patients with symptomatic, localized disease resistant to conventional treatments.

Plasmablastic lymphoma (PBL) is a rare subtype of large B-cell lymphoma most commonly seen in immunocompromised patients, particularly in those with HIV infection. In these patients, PBL often affects the oral mucosa.1 Other immunocompromised states, including immunosuppression for organ transplant and immunosenescence, have been linked to PBL.1 Epstein-Barr virus (EBV) reactivation is thought to be a major driver of PBL.1 PBL is characterized histologically by an absence of B- and T-cell markers and expression of plasma cell markers CD38 and CD138. The median overall survival of HIV-positive and HIV-negative patients with PBL is 15 months and 9 months, respectively.1 Some patients with PBL present with primary cutaneous disease (pcPBL), defined as no systemic involvement. These patients have a unique clinical presentation and an indolent course. We report the first case of iatrogenic pcPBL secondary to romidepsin therapy for primary cutaneous peripheral T-cell lymphoma not otherwise specified (pcPTCL-NOS).

Ruxolitinib is a Janus kinase 1/2 inhibitor that blocks signal transduction of interferon-gamma, a critical cytokine involved in the pathogenesis of cutaneous lichen planus (LP). In this prospective phase II study, we investigated the efficacy of topical ruxolitinib in cutaneous LP and performed transcriptomic analysis before and after therapy. Twelve patients with cutaneous LP applied topical ruxolitinib twice daily for 8 weeks. Primary endpoints were changes in total lesion count and changes in modified Composite Assessment of Index Lesion Severity score in index treated and untreated index control lesions at week 4. Total lesion count decreased by a median of 50 lesions (interquartile range 25, 723; P0.001). modified Composite Assessment of Index Lesion Severity scores decreased by a mean difference of 7.6 (standard deviation 8.8, P = 0.016) between index treated and control lesions. Type I and II interferon pathways were enriched in LP, and responsive disease displayed downregulation of interferon-stimulated genes. In this small pilot study, topical ruxolitinib was highly effective in the treatment of cutaneous LP. Transcriptomic analysis confirmed LP as an interferon-driven disease and downregulation of interferon-stimulated genes correlated with disease response.

NK/T-cell lymphomas are extremely rare lymphomas in the western world. The population of CD3+CD56+ NK/T-cells that seems to be the progenitor cells for those types of lymphomas is not homogeneous, which may explain the reason for polymorphic presentation. Several functionally distinct NK/T-cell subsets diverge after their development in the thymus. Organ-specific antigen-presenting cells may modulate NK/T-cell function and post-thymic development. The organs with the highest content of NK/T cells are tonsils, lymph nodes, spleen, skin, testis, and stomach. Not surprisingly, those are the places of the most frequent localization of NK/T-cell lymphoma. The Waldeyer’s tonsillar ring is involved most commonly. The patient sometimes may present with a single cutaneous nodule, but the asymptomatic nasal involvement could be detected on PET/CT frequently, still placing the patient into “the nasal” category. Extranasal presentation comprises around 20% of all cases and most likely arises from the dermal NK/T cells in contrast to tonsillar NK/T cells in “the nasal” cases. Unusual cases of such rare cancer are characterized by the unusual expression of non-NK/T-cell markers and rare morphologic presentations. The aberrant expression of γδ TCR on EBV+ CD56+ cells is still a matter of debate of appropriate classificational categorization. Despite semantics, the prognosis is universally gravid.

Background:Case reports suggest photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an effective treatment for refractory mycosis fungoides (MF). No prospective trials have examined the use of ALA-PDT in MF. Objective:We aimed to assess the efficacy of ALA-PDT in refractory MF. Methods:This was a prospective study at Mayo Clinic in Scottsdale, Arizona in patients ≥ 18 years with plaque-stage treatment-refractory MF. Monthly sessions of ALA with blue light PDT were administered for up to six months. Responses were measured by Composite Assessment of Index Lesion Severity (CAILS) and Physician Global Assessment (PGA). Ad hoc analysis with modified CAILS (mCAILS) was performed, eliminating hyperpigmentation from scoring. Results:Eleven patients (30 total lesions) were treated. Six patients completed the trial per protocol. Objective response rates were 36.4% by PGA (10.9-69.2%), 18.2% by CAILS (2.3-51.8%), and 36.4% by mCAILS (10.9-69.2%). Limitations:Five patients did not complete all six PDT cycles per protocol, possibly accounting for reduced efficacy. Conclusion:ALA-PDT with blue light irradiation was moderately effective and well tolerated in refractory plaque stage MF. Lower response rates compared to similar trials may be partially explained by utilization of strict lesional assessment criteria and other variations in methodology. Disclosures Mangold: MiRagen:Research Funding;Sun Pharma:Research Funding;Elorac:Research Funding;Kirin:Membership on an entity's Board of Directors or advisory committees;Solagenix:Research Funding. OffLabel Disclosure: Photodynamic therapy is a two-step therapy in which a drug that acts as a photosensitizer is administered to target a diseased tissue, followed by illumination with visible light to activate the drug and destroy the target tissue. PDT has been used to treat internal cancers as well as treatment of cancer and precancer of the skin.