Endogenous ochronosis: when clinical suspicion prevails over histopathology.

Endogenous ochronosis (EO) or alkaptonuria is an inherited autosomal recessive disease caused by the insufficiency of the enzyme homogentisic acid dioxygenase. This disturbance causes an accumulation and increased renal excretion of homogentisic acid (AHG), which manifests as dark urine when it oxidizes on contact with air. Other clinical manifestations of OE are the result of the deposit of AHG in the form of ochronotic pigment at the level of collagen in the skin and cartilage, where it causes blue-gray cutaneous hyperpigmentation, degenerative arthropathy, valvular disease, and other multisystem effects. Despite the progressive and irreversible nature of OE and the lack of a curative treatment, the life expectancy is preserved. We report a new case of EO with cutaneous and joint involvement, in which a high clinical suspicion, confirmed by elevated AHG in urine was the key in the diagnosis.

Exogenous ochronosis: the failure of depigmenting creams.

Exogenous ochronosis (EO) is an entity that manifests as black-bluish or grayish-brown cutaneous hyperpigmentation, which is a consequence of the deposition of ochronotic pigment with characteristic banana-like morphology between the collagen fibers of the dermis. Both the clinical presentation and histopathology appearance are superimposable with endogenous ochronosis or alcaptonuria, a hereditary disease in which ochronotic pigment deposition occurs at a multisystemic level. The most frequent cause of EO is the use of facial depigmenting creams containing hydroquinone, a common practice among women with high phototypes. We present a woman who developed EO on the face, upper chest, and back after prolonged use of a depigmenting cream containing hydroquinone.

Molecular Characterization, Via Next-Generation Sequencing, of Refractory or Resistant Invasive Breast Carcinoma.

The most frequently diagnosed neoplasia in the world in 2020 was breast cancer (BC). On top of its high incidence, unexpected behavior as recurrence in patients, in spite of appropriate therapies, reaches 20%-30%. We believe that some molecular characteristics of tumors may lead to this bad behavior, and we can identify them with next-generation sequencing (NGS). We made a retrospective multicentric study, conducted to molecularly characterize, by means of a custom NGS panel, cases diagnosed with treatment-refractory or treatment-resistant invasive breast carcinoma, studied in formalin-fixed paraffin-embedded (FFPE) samples. The panel included 50 genes related to tumorigenesis, cancer evolution and targeted therapies. Twelve cases were included from three centers. Alterations of driver genes were found in all of the cases, and 75% harbored mutations in TP53. Furthermore, we found alterations that could be therapeutic targets in half of the patients, such as mutations in PIK3CA (33% cases), mTOR (8.3%) or BRCA1 (8.3%). Other significant molecular alterations were: the loss of SWI-SNF complex´s components, modified genes of the MAP kinase pathway and alterations in epidermal growth factor receptor (EGFR). Not all of them are known targets but prognostic significance was found. We conclude that NGS characterization of breast cancer in FFPE samples is a reproducible technique that can provide prognostic and predictive information about our patients and therefore, constitutes, in the near future, a valuable clinical tool in the context of precision medicine.