CD73 Is an Immunometabolic Biomarker of Poor Prognosis in Patients With Primary Cutaneous Squamous Cell Carcinoma and Hematologic Malignancy.

BACKGROUND: Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. OBJECTIVE: Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. MATERIALS AND METHODS: Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good (n = 8) versus poor (n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with (n = 38) and without (n = 29) hematologic malignancy. RESULTS: Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies (p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies (p = .49). CONCLUSION: CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.

Monoclonal gammopathy in the setting of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common. Whether gammopathy is associated with PG or is an incidental finding has been debated. We sought to investigate the association and characteristics of gammopathy in patients with PG. We retrospectively identified PG patients at our institution from 2010 to 2022 who were screened for plasma cell dyscrasia. Of 106 patients identified, 29 (27%) had a gammopathy; subtypes included IgA (41%), IgG (28%), and biclonal (IgA and IgG) (14%). Mean age was similar between those with and without gammopathy (60.7 vs. 55.9 years; P = .26). In addition, hematologic or solid organ cancer developed in significantly more patients with vs. without gammopathy (8/29 [28%] vs. 5/77 [6%]; P = .003). Among the subtypes of gammopathy, IgG monoclonal gammopathy had the highest proportion of patients with subsequent cancer development (4 of 8 patients, 50%). Study limitations include a retrospective, single-institution design with a limited number of patients. Overall, our data show a high prevalence of gammopathy in patients with PG; those patients additionally had an increased incidence of cancer, especially hematologic cancer.

Serologic Biomarkers in Pemphigus Monitoring: C-reactive Protein, Macrophage Migration Inhibitory Factor, and Prolactin Levels Versus Autoantibody Assays.

Evaluation and monitoring of pemphigus vulgaris (PV) typically involve autoantibody detection by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF). We aimed to determine the levels of antipemphigus immunoglobulin (Ig) G autoantibodies using ELISA and IIF (as standard biomarkers), and compare it to prolactin, macrophage migration inhibitory factor (MIF), and C-reactive protein (CRP) (as nonstandard biomarkers) to determine which of these non-standard biomarkers is appropriate for PV monitoring. The experiment was performed before and during therapy. Anti-Dsg immunoglobulin G autoantibodies were measured using ELISA and IIF (as standard biomarkers) versus prolactin, MIF, and CRP (nonstandard), before 1 and 3 months after the treatment. Before beginning the treatment, the severity of the disease was determined using the pemphigus disease area Index (PDAI). We enrolled 60 newly diagnosed patients with PV (32 men and 28 women; mean age=43.8±14.2 years). Before treatment, the levels of anti-Dsg1, anti-Dsg3, and IIF were high and had a significant relationship with PDAI. PDAI also had a connection with the levels of CRP and prolactin. The anti-Dsg1, anti-Dsg3, IIF, and CRP titers decreased in patients treated with conventional (prednisolone plus azathioprine) and rituximab therapy during and after treatment. In conclusion, anti-Dsg1, anti-Dsg3, and IIF autoantibody titers remain standard biomarkers for assessing disease activity, severity, and PV monitoring. The trend of CRP was similar to that of anti-Dsg1, anti-Dsg3, and IIF. Thus, CRP may be used for PV monitoring.

Understanding the squamous cell carcinoma immune microenvironment.

Primary cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with a rising incidence of about 1.8 million in the United States annually. Primary cSCC is usually curable by surgery; however, in some cases, cSCC eventuates in nodal metastasis and death from disease specific death. cSCC results in up to 15,000 deaths each year in the United States. Until recently, non-surgical options for treatment of locally advanced or metastatic cSCC were largely ineffective. With the advent of checkpoint inhibitor immunotherapy, including cemiplimab and pembrolizumab, response rates climbed to 50%, representing a vast improvement over chemotherapeutic agents used previously. Herein, we discuss the phenotype and function of SCC associated Langerhans cells, dendritic cells, macrophages, myeloid derived suppressor cells and T cells as well as SCC-associated lymphatics and blood vessels. Possible role(s) of SCC-associated cytokines in progression and invasion are reviewed. We also discuss the SCC immune microenvironment in the context of currently available and pipeline therapeutics.

Recalcitrant giant orf recurrence after amputation: A case report and review of the literature.

Orf is caused by a parapoxvirus. We present a recurrent, giant digital orf case in a female patient with a history of hairy cell leukemia. In spite of shave excision, the lesion progressed and recurred after digital amputation. Treatment with topical imiquimod cream and systemic subcutaneous interferon alfa-2a was successful.

BPDAI and ABSIS correlate with serum anti-BP180 NC16A IgG but not with anti-BP230 IgG in patients with bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous disease characterized by autoantibody production against BP180 and BP230. Two scoring systems have been validated for BP including: Bullous Pemphigoid Disease Area Index (BPDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). In this study, we investigated correlations between both scoring systems and either anti-BP180 NC16A or anti-BP230 values. BPDAI and ABSIS were used to measure disease activity in 95 BP patients at Razi Hospital in Tehran, Iran. ELISA was performed on patient sera to identify any significant relationship between anti-BP180 NC16A/anti-BP230 values and BP disease activity. The two scores showed a strong correlation (ρ = 0.73; p value < 0.0001). Anti-BP180 NC16A values correlated with BPDAI (ρ = 0.49, p value = 0.0001), ABSIS (ρ = 0.47, p value < 0.0001), and BPDAI-Pruritus scores (ρ = 0.29, p value < 0.005). There was a strong correlation between anti-BP180 NC16A values and the ABSIS Skin score (ρ = 0.58, p value < 0.0001), and a moderate correlation with erosion/blister BPDAI score (ρ = 0.48, p value < 0.001) and urticaria/erythema BPDAI score (ρ = 0.27, p value = 0.009). Anti-BP230 values did not demonstrate any relationship with either scores or their subcomponents. Both scoring systems demonstrated moderate validity. Mucosal components did not show any correlation with anti-BP antibodies and are disproportionately presented in both BP scoring tools.

A Case Report of Paraneoplastic Pemphigus Associated With Retroperitoneal Inflammatory Myofibroblastic Tumor.

Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms, both malignant and benign. The most constant clinical presentation of PNP is the presence of intractable stomatitis. Herein we present a 25-year-old male with a 3-month history of refractory stomatitis especially involving the lips and widespread vesiculobullous eruption on his trunk and extremities. The diagnosis of PNP was confirmed based on histological and serological results. Investigation for the underlying neoplasm revealed a retroperitoneal tumorous mass which was biopsied and diagnosed as the inflammatory myofibroblastic tumor (IMT). The tumor was surgically excised, and different treatment regimens were used to treat the mucocutaneous lesions. Skin lesions responded favorably to treatment, but oral stomatitis still persists which is the case in most PNP patients. This combination of PNP and IMT has rarely been reported in the literature. Treatment started with corticosteroid and rituximab then tumor excised.

Temporal course of avascular femoral head necrosis in patients with pemphigus vulgaris.

BACKGROUND AND OBJECTIVES: Pemphigus vulgaris (PV) is typically treated with systemic corticosteroids and immunosuppressive agents. Avascular necrosis (AVN) of the femoral head is a well-recognized major complication of corticosteroid therapy. The characteristics of this serious complication in PV remain unknown. PATIENTS AND METHODS: Uncontrolled, retrospective study of all PV-related AVN cases diagnosed at an Iranian autoimmune bullous disease clinic between 1985 and 2013. RESULTS: Of the 2,321 medical records of PV patients reviewed, 45 (1.93 %) cases showed femoral AVN, with 30 (66.7 %) individuals being male. The mean age at diagnosis of AVN was 47.4 ± 14.2 years. The mean interval between the diagnosis of PV and the onset of AVN was 25.3 ± 18.3 months. With the exception of eight cases (17.8 %), the majority of patients developed AVN within three years after the diagnosis of PV. The mean cumulative dose of prednisolone in patients with AVN was 13,115.8 ± 7041.1 mg. There was a strong correlation between the total prednisolone dose and the time of onset of AVN (p = 0.001). In patients with a history of alendronate intake, that interval was significantly shorter (p = 0.01). CONCLUSIONS: Occurring in about 2 % of patients, AVN is a serious complication of corticosteroid treatment in patients with PV, predominantly in the first three years of treatment. In individuals receiving higher doses of prednisolone, AVN tends to occur earlier.

Zeitlicher Verlauf der avaskulären Nekrose des Hüftkopfes bei Patienten mit Pemphigus vulgaris.

HINTERGRUND UND ZIELE: Pemphigus vulgaris (PV) wird in der Regel mit systemischen Corticosteroiden und Immunsuppressiva behandelt. Avaskuläre Nekrose (AVN) des Hüftkopfes ist eine gut bekannte schwerere Komplikation einer Corticosteroid-Therapie. Die Charakteristika dieser schweren Komplikation bei PV sind nach wie vor unbekannt. PATIENTEN UND METHODEN: Nicht kontrollierte, retrospektive Untersuchung aller PV-bedingten AVN-Fälle, die in einer iranischen Klinik für bullöse Autoimmunerkrankungen zwischen 1985 und 2013 diagnostiziert wurden. ERGEBNISSE: Anhand der Krankenakten von 2321 untersuchten PV-Patienten wurden 45 Fälle (1,93 %) von femoraler AVN identifiziert. Dreißig davon waren Männer. Das mittlere Alter bei der Diagnose der AVN betrug 47,4 ± 14,2 Jahre. Der mittlere Zeitraum zwischen der Diagnose des PV und dem Einsetzen der AVN lag bei 25,3 ± 18,3 Monaten. Mit Ausnahme von acht Fällen (17,8 %) setzte die AVN bei der Mehrheit der Patienten innerhalb von drei Jahren nach Diagnose des PV ein. Die mittlere kumulative Dosis von Prednisolon bei Patienten mit AVN betrug 13.115,8 ± 7041,1 mg. Zwischen der Prednisolon-Gesamtdosis und dem Zeitraum bis zum Einsetzen der AVN bestand eine starke Korrelation (p = 0,001). Bei Patienten mit Alendronateinnahme in der Vorgeschichte war dieser Zeitraum signifikant kürzer (p = 0,01). SCHLUSSFOLGERUNGEN: Die AVN ist eine schwere Komplikation einer Corticosteroid-Behandlung bei Patienten mit PV. Sie wird bei 2 % der Patienten beobachtet und tritt vor allem in den ersten drei Behandlungsjahren auf. Bei Patienten, die höhere Dosen von Prednisolon erhalten, setzt die AVN tendenziell früher ein.