Up-regulation of SLC7A11/xCT creates a vulnerability to selenocystine-induced cytotoxicity.

The SLC7A11/xCT cystine and glutamate antiporter has emerged as an attractive target for cancer therapy due to its selective overexpression in multiple cancers and its role in preventing ferroptosis. Utilizing pharmacological and genetic approaches in hepatocellular carcinoma cell lines, we demonstrate that overexpression of SLC7A11 engenders hypersensitivity towards l-selenocystine, a naturally occurring diselenide that bears close structural similarity to l-cystine. We find that the abundance of SLC7A11 positively correlates with sensitivity to l-selenocystine, but surprisingly, not to Erastin, an inhibitor of SLC7A11 activity. Our data indicate that SLC7A11 acts as a transport channel for l-selenocystine, which preferentially incites acute oxidative stress and damage eventuating to cell death in cells that highly express SLC7A11. Hence, our findings raise the prospect of l-selenocystine administration as a novel strategy for targeting cancers that up-regulate SLC7A11 expression.

Mohs micrographic surgery versus wide local excision for eyelid melanoma: An analysis of a national database.

BACKGROUND: Although eyelid melanomas represent less than 1% of eyelid neoplasms, they have the worst prognosis. Wide local excision (WLE) and Mohs micrographic surgery (MMS) are mainstay treatment options. We conducted a retrospective analysis to assess all-cause and cause-specific mortality rates in patients undergoing WLE or MMS for eyelid melanoma. METHODS: A retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) registry was performed for eyelid melanoma treated with WLE or MMS. Cases were limited to American Joint Committee on Cancer (AJCC) stage T1 primary malignancies. RESULTS: A total of 45 cases of WLE were identified along with 48 cases of MMS for eyelid melanoma. There was no significant difference between subgroups in age group, sex, race, ethnicity, marital status at diagnosis, AJCC N stage, AJCC M stage, melanoma histology, chemotherapy use, and radiotherapy use. Among the cohort, all tumors were unilateral. Kaplan-Meier analysis with log-rank demonstrated no significant difference between MMS and WLE subgroups with regard to overall survival (P = 0.662) and cancer-specific survival (P = 0.494). Cox regression adjusting for variables with α<0.10 and found no significant difference in all-cause mortality (HR, 0.923; 95% CI 0.310-2.747; P = 0.885) or cancer-specific mortality (HR, 0.518; 95% CI 0.047-5.711; P = 0.591) when patients who underwent MMS were compared to those who underwent WLE. CONCLUSION: While our study is limited by a small number of patients, our analysis demonstrated no significant difference in all-cause or cause-specific survival for patients with eyelid melanoma treated with MMS compared with WLE. In areas requiring preservation of tissue due to cosmetic or functional purposes, MMS is a reasonable surgical approach.

Myonecrosis complicating uncontrolled diabetes mellitus.

A 37-year-old woman with uncontrolled type 1 diabetes mellitus and end-stage renal disease presented to our hospital with 10 days of severe left thigh pain. Physical examination revealed warmth, swelling, and tenderness of the left anterior and medial thigh. Workup revealed a mildly elevated creatinine kinase. Magnetic resonance imaging without contrast revealed diffuse extensive soft tissue edema and a heterogeneous, tubular fluid collection within the adductor magnus. Needle aspiration revealed hematoma and myonecrosis. Cultures and cytology were negative. A diagnosis of diabetic myonecrosis was made. Myonecrosis is a rare complication of diabetes, and the gold standard for diagnosis is tissue biopsy. However, magnetic resonance imaging may be sensitive and specific for diagnosis and prevent morbidity.

Association of Flame-Retardant Clothing With Mycosis Fungoides: A Retrospective Analysis.

Introduction: Mycosis fungoides (MF), the most prevalent form of cutaneous T-cell lymphoma (CTCL), has been associated with a variety of environmental and occupational exposures. Flame-retardant clothing (FRC), in contrast to flame-resistant clothing, is chemically treated and may constitute a previously unrecognized occupational hazard. Objectives: To report an association between FRC and MF. Methods: After encountering several young male patients whose onset of MF coincided with the occupational use of FRC and occupation as fire fighters, we did a retrospective search. Additional biopsy proven MF patients with use of FRC were identified by the EPIC electronic medical record using the search terms "CTCL, mycosis fungoides, flame, and flame-retardant." Results: Eight MF patients, all males, ranging in age from 31 years to 64 years (median age, 35 years) with exposure to FRC were identified. MF remission was noted in three patients who discontinued FRC use and in one patient who used a cotton undershirt barrier, while disease persistence was noted in one patient who continued to use FRC. Conclusions: FRC appears to be associated with development of MF through chronic antigen stimulation. Use of FRC is an occupational hazard for fire fighters. Any patient whose MF coincides with use of FRC should avoid further exposure through avoidance or switching to clothing made from inherently flame-resistant fibers.

Hypercalcemia as the Initial Presentation of Acute T-cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a T-cell malignancy that generally presents with widespread involvement of lymph nodes, peripheral blood, and/or skin. It is an uncommon malignancy linked to the human T-lymphotropic virus 1 (HTLV-1). Herein, we present a case of ATLL that was diagnosed after a patient presented to our hospital with nonspecific symptoms of fatigue and weakness and was subsequently found to have hypercalcemia secondary to his blood malignancy. We engage in a discussion of the etiology, epidemiology, and management of patients with this rare malignancy as well as the mechanisms that result in hypercalcemia.

Sebaceous Carcinoma Masquerading As Orbital Cellulitis.

Sebaceous cell carcinoma is an uncommonly encountered cutaneous malignancy. Often considered a great masquerader, sebaceous cell carcinoma arises from meibomian glands and can have a poor prognosis if not diagnosed early. In this case report, we present a patient with sebaceous cell carcinoma who presented to our emergency department with a clinical presentation that was concerning for orbital cellulitis. The patient was initially started on intravenous antibiotics. However, workup, including imaging and laboratory results, pointed toward malignancy as the diagnosis. The patient underwent an incisional biopsy and pathology confirming the diagnosis of sebaceous cell carcinoma. We engaged in further discussion of this peculiar cutaneous masquerader, differential diagnoses, and important considerations.

Severe Combined Immunodeficiency with De Novo Duchenne Muscular Dystrophy Mutation.

Both severe combined immunodeficiency (SCID) syndrome and Duchenne muscular dystrophy (DMD) are rare conditions. Patients with X-linked SCID have pathogenic variants of the IL2RG gene, resulting in defective cellular and humoral immunity. DMD is also an X-linked condition caused by a dystrophin gene mutation, causing progressive proximal muscle weakness. We present a patient diagnosed with SCID at birth who underwent matched unrelated donor bone marrow transplant (BMT). Several months after, he was noted to have persistently elevated aminotransferases. Despite a lack of clinical signs of graft versus host disease (GvHD), a liver biopsy revealed mild GvHD. Creatine kinase (CK) levels of >19,000 U/L prompted evaluation for muscular dystrophies. Given BMT, genetic analysis was not an option. Muscle biopsy confirmed DMD. This case highlights the complexity of diagnosing and managing uncommon genetic conditions through a multidisciplinary team-based approach. This case is only the second reported case of SCID and DMD together.

Disseminated Nonsegmental Vitiligo Associated With Halo Nevi and Premature Gray Hair.

Halo nevi (HN) are acquired melanocytic nevi circumferentially surrounded by a depigmented patch. HN are commonly associated with vitiligo and can be associated with uveal, mucosal, or cutaneous melanoma in certain patient populations. HN may also have localized leukotrichia of terminal hair overlying the nevus. We report a less common triad of rapid-onset HN, nonsegmental vitiligo, and premature hair graying (PHG) of scalp hair.

Second primary malignancies after ocular adnexal lymphoma diagnosis.

BACKGROUND: Although studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated this risk in patients with lymphoma originating within the ocular adnexa. We conducted a retrospective study to assess incidence of secondary malignancies in patients with a prior diagnosis of ocular adnexal lymphoma (OAL) and to determine latency periods and age-groups at increased risk for SPM occurrence. METHODS: Retrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results (SEER) 9 database. Patients with an initial primary malignancy diagnosis of OAL between 1973 and 2015 were included in the study. Standardized incidence ratios (SIR) and excess absolute risks (EAR) compared to a SEER reference population with similar sex, race, age, and calendar year were computed for SPMs. Excess absolute risk is per 10,000 individuals; alpha of 0.05 was used. RESULTS: Of 1834 patients with primary ocular adnexal lymphoma, 279 developed a secondary malignancy during average follow-up of 110.03 months (+/- 88.46), denoting higher incidence than expected (SIR 1.20; 95% CI, 1.07 to 1.35; EAR 30.56). Amongst the primary lymphoma cohort, 98.7% (1810/1834) of patients had non-Hodgkin's lymphoma and amongst those that developed secondary malignancies, 99.6% (278/279) had non-Hodgkin's lymphoma. Patients exhibited increased incidence of lymphohematopoietic and non-lymphohematopoietic second malignancies and no secondary malignancies of the eye or orbit. Patients had increased incidence of secondary malignancies in the first year (SIR 2.07; 95% CI, 1.49 to 2.79; EAR 150.37) and 1-5 years following lymphoma diagnosis (SIR 1.24; 95% CI, 1.01 to 1.51; EAR 34.89). Patients with various OAL subtypes demonstrated differing patterns of site-specific and overall SPM risk. CONCLUSIONS: Patients with prior diagnosis of ocular adnexal lymphoma possess increased risk of hematologic and non-hematologic secondary malignancies. Risk of secondary malignancy could vary by lymphoma subtype. Patients with ocular adnexal lymphoma may benefit from regular surveillance to promote early detection of second primary malignancies.

Association of Gender with Survival in Melanoma In Situ of the Head and Neck: A National Database Study.

Introduction While prior studies have addressed the gender-specific survival of malignant melanoma, such investigation is lacking for melanoma in situ (MIS) and for the sun-exposed head and neck areas. Understanding the role of patient characteristics on disease prognosis is essential in determining optimal patient treatment and follow-up. We conducted a retrospective cohort study of patients diagnosed with MIS of the head and neck to assess the association of gender with long-term survival. Methods First primary cases of MIS diagnosed between 1998 and 2015 were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis adjusting for demographic, tumor, and treatment characteristics was used to evaluate all-cause and cancer-specific mortality risks. Results After adjusting for demographic, tumor, and treatment data, males demonstrated significantly poorer overall survival (hazard ratio [HR] 1.484; 95% confidence interval [CI] 1.332, 1.653; P<0.001) and cancer-specific survival (HR 1.571; 95% CI 1.056, 2.338; P=0.026) compared to their female counterparts. Conclusion Proposed reasons for these findings include gender-based hormonal influence on cancer growth and development, gender-specific health utilization behaviors, and gender-based cosmetic impact of cutaneous malignancies. These findings do have limitations, including its retrospective nature, possible upgrading of MIS diagnoses during the study period, miscoding, and inability to account of lifestyle/modifiable/environmental risk factors. Nevertheless, it suggests a gender-specific survival difference, which may be further investigated and considered as part of clinician awareness, influence patient counseling, and screening for such patients.

Procalcitonin to Distinguish Viral From Bacterial Pneumonia: A Systematic Review and Meta-analysis.

Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37-.71; I2 = 95.5%) and 0.76 (95% CI, .62-.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP.