Value of PD-L1, PD-1, and CTLA-4 Expression in the Clinical Practice as Predictors of Response to Nivolumab and Ipilimumab in Monotherapy in Patients With Advanced Stage Melanoma.

BACKGROUND: The introduction of immune checkpoint inhibitors (ICI) has improved the survival outcomes of patients with advanced melanoma. To date, only a few studies have evaluated the immunohistochemical (IHC) expression of PD-1 and CTLA-4 in tumor-infiltrating lymphocytes (TILs) as predictive markers of response to ICI, most of them in the context of clinical trials. Moreover, the predictive value of PD-L1 in melanoma cells in the response to immunotherapy is unclear. The aim of our study was to assess the IHC expression of PD-L1, PD-1, and CTLA-4 in samples of patients with advanced melanoma and to establish their prognostic value as predictors of ICI response in a university hospital. METHODS: The expression of PD-L1, PD-1, and CTLA-4 was evaluated in pretreatment tumor samples in a series of 35 patients, 21 patients treated with nivolumab and 14 patients with ipilimumab in monotherapy. RESULTS: In the nivolumab group, 4 tumors (19%) were positive for PD-L1 and all of them showed a partial response to the treatment. However, 4 patients whose tumors did not express PD-L1 also responded to nivolumab. PD-1 expression was not associated with better progression-free survival (PFS). In the ipilimumab group, 5 patients (35.7%) showed expression of CTLA-4. Positive cases showed a better PFS; however, one negative case responded to ipilimumab. CONCLUSIONS: Nivolumab produces a better response compared with ipilimumab in patients with melanoma. The IHC expression of PD-L1 and CTLA-4 are associated with a higher response rate to nivolumab and ipilimumab, respectively, and better PFS, but the existence of responder patients with negative expression suggests that they are not adequate biomarkers to select candidate patients for ICI in the clinical practice.

Familial papular epidermal nevus with "skyline" basal cell layer.

Papular epidermal nevus with "skyline" basal cell layer is a variant of keratinocytic nevus that usually occurs sporadically but may affect different family members. We report on the fourth family with papular epidermal nevus with "skyline" basal cell layer affecting a 3-month-old girl and her father.

Cutaneous adenodermatofibroma: report of 2 cases.

Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.

Síndrome de Stevens-Johnson/necrolisis epidérmica tóxica tratado con inmunoglobulinas intravenosas / Stevens-Johnson Syndrome/Toxic epidermal necrolysis treated with intravenous immunoglobulins

El síndrome de Stevens-Johnson (SSJ) y la necrolisis epidérmica tóxica (NET) se engloban dentro de un mismo espectro de enfermedad, pues sólo se diferencian por el grado de despegamiento cutáneo. En la NET se ve afectada más del 30 % de la superficie corporal, por lo que se convierte en un proceso grave cuya frecuencia se estima en 1,2-6 casos por millón de habitantes y año. Se describe a un varón de 75 años que sufrió un SSJ con evolución a NET, probablemente por la ingesta de extracto de ginkgo biloba. Fue tratado con inmunoglobulinas intravenosas, con dosis de 0,5 g/kg/día durante 5 días consecutivos, con evolución favorable y sin efectos secundarios relevantes. Es evidente que casos aislados no justifican el uso sistemático de este tratamiento, pero pueden contribuir a una mayor experiencia

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are part of the same disease spectrum, but are differentiated by the degree of skin detachment. In TEN, more than 30 % of the body's surface area is affected; thus, it is a serious process, whose frequency is estimated at 1.2-6 cases per million population/year. We describe the case of a 75-year-old male who suffered from SJS which evolved into TEN, probably because of the ingestion of ginkgo biloba extract. He was treated with intravenous immunoglobulins (Ig IV) at a dose of 0.5 g/kg/day for five consecutive days, with favorable progress and no significant side effects. It is evident that isolated cases do not justify the systematic use of this treatment, but they may help build up experience

Hipertricosis lanuginosa adquirida paraneoplásica / Acquired paraneoplastic hypertrichosis lanuginosa

La hipertricosis lanuginosa adquirida, un proceso paraneoplásico poco frecuente, consiste en el desarrollo rápido de pelo tipo lanugo, fundamentalmente en cara. Se describe una mujer de 50 años con hipertricosis en cara y porción superior del cuerpo de 4 meses de evolución y pérdida de peso en los últimos 6 meses, en la que se detectó la presencia de un carcinoma epidermoide de cuello uterino inoperable. La hipertricosis lanuginosa es un indicador de mal pronóstico. Se asocia a tumores de cualquier localización, pero con mayor frecuencia, pulmonares y colorrectales. Este caso es el primero asociado a carcinoma epidermoide de cuello uterino

Acquired hypertrichosis lanuginosa, an infrequent, paraneoplastic process, consists of the rapid development of lanugo-type hair, primarily on the face. We describe a 50-year-old woman with a 4-month case of hypertrichosis on the face and upper body, and weight loss over the last 6 months, in whom an inoperable squamous cell carcinoma of the cervix was discovered. Hypertrichosis lanuginosa is an indicator of a poor prognosis. It is associated with tumors in any location, but most often with lung and colorectal tumors. This is the first case associated with squamous cell carcinoma of the cervix

[Acquired paraneoplastic hypertrichosis lanuginosa]. / Hipertricosis lanuginosa adquirida paraneoplásica.

Acquired hypertrichosis lanuginosa, an infrequent, paraneoplastic process, consists of the rapid development of lanugo-type hair, primarily on the face. We describe a 50-year-old woman with a 4-month case of hypertrichosis on the face and upper body, and weight loss over the last 6 months, in whom an inoperable squamous cell carcinoma of the cervix was discovered. Hypertrichosis lanuginosa is an indicator of a poor prognosis. It is associated with tumors in any location, but most often with lung and colorectal tumors. This is the first case associated with squamous cell carcinoma of the cervix.

[Stevens-Johnson syndrome/toxic epidermal necrolysis treated with intravenous immunoglobulins]. / Síndrome de Stevens-Johnson/necrolisis epidérmica tóxica tratado con inmunoglobulinas intravenosas.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are part of the same disease spectrum, but are differentiated by the degree of skin detachment. In TEN, more than 30 % of the body's surface area is affected; thus, it is a serious process, whose frequency is estimated at 1.2-6 cases per million population/year. We describe the case of a 75-year-old male who suffered from SJS which evolved into TEN, probably because of the ingestion of ginkgo biloba extract. He was treated with intravenous immunoglobulins (Ig IV) at a dose of 0.5 g/kg/day for five consecutive days, with favorable progress and no significant side effects. It is evident that isolated cases do not justify the systematic use of this treatment, but they may help build up experience.