Therapy of advanced squamous cell carcinoma of the skin.

Advanced unresectable squamous cell carcinoma of the skin (SCCS) is a rare condition, which is difficult to treat. Because of its rarity, few therapeutic trials are available. Moreover, SCCS often occur in elderly. Conventional treatment options for advanced SCCS are chemotherapy mainly with cisplatin-based regimens. Immunotherapy with interferon alpha and retinoids combination was also shown to be efficient. Toxicity of these treatments limits, however, their use in elderly patients and an initial work up for a global assessment is needed in order to adapt the choice. More recently, epithelial growth factor receptor (EGFR) targeted therapies have been developed and induced interesting response rates in small series of patients with unresectable SCCS. Their efficacy in SCCS must be confirmed by larger phase III trials and the identification of predictive biological factors of response is warranted. New therapeutic approaches combining EGFR inhibitors either with IGFR inhibitors, or immunomodulators or inhibitors of the PI3K/AKT/mTOR pathway are currently under evaluation in head and neck carcinomas and might represent valuable therapeutic approaches for unresectable SCCS. Moreover, there are several new molecular candidate treatment targets for unresectable SCCS including somatic NOTCH1 or NOTCH2 inactivating mutations, ALK1, which could be a good candidate for antiangiogenic therapy and matrix metallopeptidase 7, which enhances proliferation, migration, and invasion of cancer cells. Organ transplant recipients often develop SCCS and in some patients, SCCS are rapidly progressing. Management of SCCS in this subgroup of patients includes both carcinologic treatment and modification of immunosuppression. Specific treatment is generally the same as in immunocompetent patients. Switching from calcineurin inhibitors to sirolimus or reducing immunosuppression has to be considered.

Specific Patterns of Blood ILCs in Metastatic Melanoma Patients and Their Modulations in Response to Immunotherapy.

Immunotherapy targeting immune checkpoint receptors brought a breakthrough in the treatment of metastatic melanoma patients. However, a number of patients still resist these immunotherapies. Present on CD8+T cells, immune checkpoint receptors are expressed by innate lymphoid cells (ILCs), which may contribute to the clinical response. ILCs are composed of natural killer (NK) cells, which are cytotoxic effectors involved in tumor immunosurveillance. NK cell activation is regulated by a balance between activating receptors that detect stress molecules on tumor cells and HLA-I-specific inhibitory receptors. Helper ILCs (h-ILCs) are newly characterized ILCs that secrete cytokines and regulate the immune homeostasis of tissue. We investigated the modulation of blood ILCs in melanoma patients treated with ipilimumab. Circulating ILCs from metastatic stage IV melanoma patients and healthy donors were studied for their complete phenotypic status. Patients were studied before and at 3, 6, and 12 weeks of ipilimumab treatment. A comparison of blood ILC populations from donors and melanoma patients before treatment showed changes in proportions of ILC subsets, and a significant inverse correlation of CD56dim NK cells and h-ILC subsets was identified in patients. During treatment with ipilimumab, percentages of all ILC subsets were reduced. Ipilimumab also impacted the expression of the CD96/TIGIT/DNAM-1 pathway in all ILCs and increased CD161 and CTLA-4 expression by h-ILCs. When considering the response to the treatment, patients without disease control were characterized by higher percentages of CD56bright NK cells and ILC1. Patients with disease control displayed larger populations of activated CD56dimCD16+ DNAM-1+ NK cells, while anergic CD56dimCD16-DNAM-1- NK cells were prominent in patients without disease control. These results provide original findings on the distribution of ILC subsets in advanced melanoma patients and their modulation through immunotherapy. The effects of ipilimumab on these ILC subsets may critically influence therapeutic outcomes. These data indicate the importance of considering these innate cell subsets in immunotherapeutic strategies for melanoma patients.

Sífilis nodular diseminada con fenómeno de prozona asociada a VIH/sida / Nodular syphilis spread associated with HIV/AIDS prozone phenomenon

Los cuadros de sífilis nodular diseminada que se presentan como un pseudolinfoma son muy raros, se ha descrito hasta la actualidad 11 casos publicados. La coinfección con el VIH puede alterar los resultados de las pruebas treponémicas y no treponémicas, lo que resulta en hallazgos falsos negativos y falsos positivos. Se estima que la coinfección sífilis y VIH está en aumento, por lo que se necesitaun diagnóstico acertado para evitar las graves consecuencias de un diagnóstico tardío. Presentamos un caso de sífilis nodular que sepresentó como un pseudolinfoma en un paciente con infección por VIH/sida que inicialmente mostró serología para sífilis negativaatribuida al fenómeno de prozona.

Disseminated nodular syphilis boxes presenting as a pseudo-lymphoma nodular are very rare, to date only 11 reported cases has been described. Co-infection with HIV may alter the results of the tests nontreponemal and treponemal not, resulting in false negative. It is estimated that co-infection HIV and syphilis is on the rise, so a correct diagnosis is needed to prevent the serious consequences of a late diagnosis. We present a case of nodular syphilis which was presented as a pseudolymphoma in a patient with HIV/AIDS infection that initially showed a serology for syphilis negative attributed to the prozone phenomenon.

Sarcoma de Kaposi clásico / Classic Kaposi´s sarcoma

El Sarcoma de Kaposi (SK) es una neoplasia del endotelio vascular, inicialmente descrita por Moritz Kaposi en 18721. Ha sido clasificado en cuatro grupos epidemiológicos: clásico, endémico (africano), iatrogénico (relacionado con tratamiento inmunosupresor) y epidémico (asociado a infección por virus de inmunodeficiencia humana - VIH); cada uno de ellos con características clínicas y patológicas singulares, aunque todos tienen relación con el virus herpes humano 8 (VHH-8), el cual es necesario pero no suficiente para producir la enfermedad. Las descripciones de SK clásico son más usuales en varones adultos de ascendencia judía y con un curso tardío. En el Perú se han reportado casos de SK endémico y epidémico, así como una elevada seroprevalencia de VHH-8. Se presenta el caso de un paciente con el diagnóstico de SK con inmunomarcación para VHH-8 y con un curso prolongado de enfermedad.

The Kaposi's sarcoma (KS) is a neoplasia of vascular endothelium, initially described by Moritz Kaposi in 18721. It has been classified into four epidemiological groups: classic, endemic (African), iatrogenic (related to immunosuppressive treatment) and epidemic (associated with infection by human immunodeficiency virus - HIV); each with unique clinical and pathological characteristics, although all have a connection with the human herpes virus 8 (HHV-8), which is necessary but not sufficient to produce the disease. The cases of classic KS are more common in jewish descent men, and they have a delayed course. In Peru, there have been reports of endemic and epidemic cases of KS, as well as a high seroprevalence of HHV-8. We present a case of a patient diagnosed with SK with positiveness to HHV-8 and with a prolonged course of illness.

Verruga peruana en fase involutiva presentándose como pseudolinfoma / Involution phase peruvian wart presenting as pseudolymphoma

El espectro clinico de la infección por Bartonella bacilliformis varia ampliamente desde una infección subclínica hasta una enfermedad aguda fulminante, con hemólisis severa o desarrollo insidioso de tumores vasculares de la piel, con poca o ninguna sintomatología. Se reporta un caso enfermedad de Carrión presentándose como una tumoración única de aspecto angiomatoso, sin antecedente de enfermedad aguda previa, y con hallazgos histológicos compatibles con pseudolinfoma cutáneo, en la que la coloración de Warthin Starry nos permitió visualizar al agente infeccioso.

The clinical spectrum of Bartonella bacilliformis infection varies widely from subclinical infection to acute fulminant disease with severe hemolysis or insidious development of vascular tumors of the skin, with little or no symptoms. We report a case of Carrion's disease presenting as a single angiomatous tumor, with no history of previous symptoms, and histological findings consistent with cutaneous pseudolymphoma in which Warthin Starry staining allowed us to visualize the infectious agent.