Isolated primary sebaceous gland carcinoma of the bulbar conjunctiva.

Purpose: To report a rare case of primary sebaceous gland carcinoma of the bulbar conjunctiva without palpebral involvement. Observation: A 76-year-old male was referred to the cornea service for a suspicious lesion on the limbal conjunctiva and cornea of his left eye. On exam, there was a large fibrovascular growth with conjunctivalization of the cornea from 2:00 to 10:00 extending 6mm onto the cornea. Patient underwent treatment with 5-fluouracil, followed by excisional biopsy with cryotherapy. Histopathologic examination demonstrated poorly differentiated sebaceous gland carcinoma. Subsequent map biopsies of the palpebral and bulbar conjunctiva of the left eye were performed and ruled out pagetoid spread. Conclusions and Importance: Primary sebaceous gland carcinoma of the bulbar conjunctiva without eyelid involvement is a rare phenomenon. Our patient joins a few case reports in the literature. Of these cases, we are the second case to utilize 5-flurouracil preoperatively. We recommend clinicians consider sebaceous carcinoma on their differential when ocular surface neoplasms diagnosed as other conditions do not respond to conventional therapies.

Spontaneous orbital hemorrhage in a case of acute liver failure.

Purpose: To report an unusual case of spontaneous orbital hemorrhage in the setting of DIC and hepatic failure. Observations: A 33-year-old female presented to the Emergency Department (ED) with acute liver failure. During the first week of her hospital admission, she developed unilateral eyelid swelling and proptosis, prompting a consult to ophthalmology. Additional physical examination revealed significantly decreased visual acuity, extraocular muscle restriction, afferent pupillary defect, and increased intraocular pressure. Computed tomography (CT) and ultrasound confirmed the diagnosis of intraorbital hemorrhage. Aggressive management in the form of lateral canthotomy, cantholysis, and septolysis was unable to be performed due to the patient's multiple comorbidities outweighing the potential benefits. Conclusions and importance: This rare phenomenon is unique from previous existing literature in that the timing of the incident limited the therapeutic options for this patient, additional imaging in the form of ultrasound was utilized in the work-up, and to our knowledge this is the second case of spontaneous orbital hemorrhage as a complication of disseminated intravascular coagulation (DIC) caused by hepatic failure.

Age and insulin-like growth factor-1 impact PCNA monoubiquitination in UVB-irradiated human skin.

Nonmelanoma skin cancers occur primarily in individuals over the age of 60 and are characterized by an abundance of ultraviolet (UV) signature mutations in keratinocyte DNA. Though geriatric skin removes UV photoproducts from DNA less efficiently than young adult skin, it is not known whether the utilization of other prosurvival but potentially mutagenic DNA damage tolerance systems such as translesion synthesis (TLS) is altered in older individuals. Using monoubiquitination of the replicative DNA polymerase clamp protein PCNA (proliferating cell nuclear antigen) as a biochemical marker of TLS pathway activation, we find that UVB exposure of the skin of individuals over the age of 65 results in a higher level of PCNA monoubiquitination than in the skin of young adults. Furthermore, based on previous reports showing a role for deficient insulin-like growth factor-1 (IGF-1) signaling in altered UVB DNA damage responses in geriatric human skin, we find that both pharmacological inhibition of the IGF-1 receptor (IGF-1R) and deprivation of IGF-1 potentiate UVB-induced PCNA monoubiquitination in both human skin ex vivo and keratinocytes in vitro. Interestingly, though the TLS DNA polymerase Pol eta can accurately replicate the major photoproducts induced in DNA by UV radiation, we find that it fails to accumulate on chromatin in the absence of IGF-1R signaling and that this phenotype is correlated with increased mutagenesis in keratinocytes in vitro. Thus, altered IGF-1/IGF-1R signaling in geriatric skin may predispose epidermal keratinocytes to carry out a more mutagenic form of DNA synthesis following UVB exposure.

A Case of Orbital Granuloma Secondary to Dermal Filler Injection.

A foreign body granulomatous reaction is a rare complication of the subcutaneous injection of fillers. We describe a 57-year-old female that presented with a six-month history of a non-painful, right lower eyelid mass. She had a dermal filler in the zygomatic region several months before the onset of her symptoms. Anterior orbitotomy and pathology revealed multinuclear giant cells consistent with a hyaluronic acid-based filler. This case describes the clinical presentation, histopathologic features, and treatment of an orbital granuloma secondary to dermal filler injection. Our case was uncommon because the zygomatic filler migrated across the orbital septum. Additionally, transconjunctival orbitotomy was used instead of a hyaluronidase injection due to the inferior location of the granuloma.

Spironolactone and XPB: An Old Drug with a New Molecular Target.

Spironolactone (SP) is commonly used for the treatment of heart failure, hypertension, and complications of cirrhosis by antagonizing the mineralocorticoid receptor. However, SP also antagonizes the androgen receptor, and thus SP has also been shown to be effective in the treatment of acne, hair loss, and hirsutism in women. Interestingly, recent drug repurposing screens have identified new and diverse functions for SP as a simulator of tumor immunosurveillance and as an inhibitor of DNA repair and viral infection. These novel pharmacological effects of SP have all been linked to the ability of SP to induce the rapid proteolytic degradation of the xeroderma pigmentosum group B (XPB) protein. XPB is a critical enzymatic component of the multi-subunit complex known as transcription factor II-H (TFIIH), which plays essential roles in both DNA repair and the initiation of transcription. Given the critical functions for XPB and TFIIH in these processes, the loss of XPB by SP could lead to mutagenesis. However, the ability of SP to promote cancer stem cell death and facilitate immune recognition may counteract the negative consequences of SP to mitigate carcinogenic risk. Thus, SP appears to have new and interesting pharmacological effects that may extend its potential uses.