Taxanes-induced cutaneous eruption: another histopathologic mimicker of malignancy.

BACKGROUND: Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation. OBJECTIVES: We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically. METHODS: Cutaneous biopsies were obtained in each patient. RESULTS: Atypical starburst-like or ring-like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case. DISCUSSION: These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under-reported. CONCLUSION: Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.

Amyophatic dermatomyositis presenting as a flagellated skin eruption with positive MDA5 antibodies and thyroid cancer: a real association?

Amyopathic dermatomyositis (ADM) is characterized clinically by typical skin lesions with hypomyopathy or no muscular involvement. ADM has been recently reported to be complicated by rapidly progressive interstitial lung disease (ILD), especially in patients with positive antibodies against melanoma differentiation-associated gene 5 (MDA5). These patients may have a low risk of cancer, but no clinical, histological or laboratory markers completely specific for paraneoplastic DM have been identified to date. We report a case of flagellate erythema as the initial presentation of ADM associated with ILD, positive MDA5 antibodies and a concomitant diagnosis of thyroid cancer. We discuss the unusual clinical features and associations that make this case particularly interesting.

[Proliferative cutaneous epithelioid angiomatous nodule]. / Nódulo angiomatoso epitelioide cutáneo proliferativo.

The cutaneous epithelioid angiomatous nodule is an uncommon benign vascular proliferation that has only recently been described. Clinically, it usually presents as a solitary, fast-growing, small reddish papulous or nodular lesion on the trunk or limbs of adults. Histopathologic study reveals a proliferation of epithelioid cells and predominantly solid, well delimited, unilobular growth in the superficial dermis. Well defined vessels are often found permeating the lesion, which also shows a certain degree of inflammatory infiltration. The cells contain abundant pink cytoplasm, often with vacuoles, and vesicular nuclei with prominent nucleoli. The morphology of these cells is relatively uniform, without atypia or pleomorphism, although mitoses are not uncommon. We report 2 new cases of cutaneous epithelioid angiomatous nodules, the first in a 28-year-old pregnant woman and the second in a 27-year-old man. In both cases, the usual characteristics of this entity were present, but with the peculiarity of a high mitotic index. We discuss the differential diagnosis of cutaneous epithelioid angiomatous nodules with other vascular proliferations that exhibit epithelioid cytology.

[Trichilemmal horn: a new case and review of the literature]. / Cuerno tricolémico: presentación de un nuevo caso y revisión de la literatura.

Trichilemmal horn, or trichilemmal keratosis, is an uncommon benign neoplasm of follicular lineage with trichilemmal differentiation. The essential characteristics of this tumor are its clinical presentation in the form of a cutaneous horn with trichilemmal keratinization apparent in the histology study (with a hyperplastic epithelium giving rise to dense, orthokeratotic eosinophilic keratin). We present a new case of this type of tumor in an 82-year-old woman who developed a solitary lesion on her scalp after surgical removal of a trichilemmal cyst. On the basis of the pathology report, the tumor was diagnosed as trichilemmal horn. We review the 33 reports of this tumor in the literature to date.

[Importance of heterotrimeric G proteins in prostate cancer molecular biology]. / Importancia de las proteínas G heterotriméricas en la biología molecular del cáncer de próstata.

OBJECTIVE: To deep in the knowledge of the involvement of G-protein alphas and alphai subunits in human prostate cancer. METHODS: Prostate tissue from 9 patients undergoing radical prostatectomy for prostate cancer and 5 controls undergoing cystoprostatectomy for bladder carcinoma. G-protein alphas and alphai subunits were studied for expression (mRNA by RT-PCR and protein by Western-blot), functionality (adenylyl cyclase activity, AC) and possibility of mutations (analysis with restriction enzymes and cDNA sequentiation). RESULTS: At mRNA level, the expression of alphas, alphai1, alphai2 y alphai3 was detected in healthy and cancerous tissues. At protein level, the expression of alphas y alphai1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of alphai3/0 also diminished, whereas that of beta subunit was not modified. Basal AC activity in adenocarcinoma membranes was 40% inferior to the control. Digestion with restriction enzymes Eag I or AlwN I did not allow to locate mutations in alphas. However, digestion at alphai2 level with BstU I enzyme served to observe a change of Gln205 (CAG triplet) to Pro (CCG). CONCLUSIONS: The functionality and expression of heterotrimeric G proteins are selectively modified in human prostate adenocarcinoma, occurring in addition some punctual mutation. The observed substitution of Gln205 by Pro may result in a low GTPase activity for alphai2 that, therefore, is stabilized in its active form.

A two-year study on the effects of nicotine and its withdrawal on mood and sleep.

Acute administration of nicotine has beneficial effects on a variety of neurological and psychiatric disorders. The purpose of this study was to determine the long-term effects of transdermal nicotine on sleep and major depression. Under a single blind protocol study where patients initially received nicotine and then switched to placebo. Fourteen non-smoking patients with major depression (Hamilton Rating > or = 18) served as subjects. Transdermal nicotine (17.5 mg), was administered five days weekly for six months, three days weekly on month 7 and one day per week on month 8. From the 9th to the 24th month, once a week a patch without nicotine substituted the nicotine patch. Sleep and depression was assessed throughout. REM sleep latency changed from 32.6 min. to 78.2 min. at the end of the study, wakefulness decreased, slow wave sleep increased throughout the study and a transient decrease of REM sleep duration upon nicotine withdrawal was observed. Hamilton scores went from an initial mean score of 29.7 to a final score of 10.8. The results support the possible therapeutical effects of long-term transdermal nicotine on sleep and mood, with a carryover effect into the withdrawal period, even though, the conclusions should be taken with caution due to the design applied.

Estudio del sueño su historia / History of the study of sleep

El conocimiento de los mecanismos fisiológicos del sueño y de su patología ha tenido un gran desarrollo a par de la segunda mitad del siglo XX; sin embargo, existen documentos que desde el siglo XVII marcan el inicio de I electrofisiología. La técnica actual para el estudio del sueño es la polisomnografía que consiste en una serie de estudios electrofisiológicos realizados de manera simultánea; a partir de esta técnica es posible observar cambios en el funcionamiento del organismo ocurren mientras dormimos y permiten establecer con precisión la presencia de distintas etapas de sueño, así como los factores subyacentes a las distintas patologías del dormir. La polisomnografía se ha desarrollado a partir de la electrofisiología, de tal manera que es importante conocer la, evolución de ambas disciplinas para lograr una mejor comprensión del estudio actual de la medicina del sueño. En la presente revisión se hace un análisis de lo hechos más relevantes que han determinado el avance del conocimiento del sueño tanto desde el punto de vista básico como clínico.

Obstructive sleep apnea secondary to surgery for velopharyngeal insufficiency.

The files of 585 patients who had had pharyngeal flap surgery for the correction of velopharyngeal insufficiency were reviewed. Eighteen patients, ranging in age from 6 to 16 years, showed clinical symptoms of obstructive sleep apnea syndrome. All of these cases had a polysomnographic evaluation and videonasopharyngoscopy. Fifteen cases met the criteria for the diagnosis of obstructive sleep apnea syndrome and eventually underwent surgical treatment. A modified uvulopalatopharyngoplasty was done in 14 of the 15 cases. One patient had a prominent uvula flipping into the port of a Jackson's type pharyngoplasty, so a partial resection of the uvula was performed. Surgical treatment was successful in 14 of 15 cases, including the case with the partial uvular resection. In one case, severe sleep apnea persisted after surgery and a complete section of the flap was performed to correct the obstruction. Sizeable tonsils were found in 13 out of 15 cases, whereas flap width appeared unrelated to obstruction. Preoperative assessment of tonsillar tissue is of vital importance before pharyngeal flap surgery.

Differential expression of two genes encoding isoforms of the ATPase involved in sodium efflux in Saccharomyces cerevisiae.

The ENA2 gene encoding a P-type ATPase involved in Na+ and Li+ effluxes in Saccharomyces cerevisiae has been isolated. The putative protein encoded by ENA2 differs only in thirteen amino acids from the protein encoded by ENA1/PMR2. However, ENA2 has a very low level of expression and for this reason did not confer significant Li+ tolerance on a Li+ sensitive strain. ENA1 and ENA2 are the first two units of a tandem array of four highly homologous genes with probably homologous functions.

Activation of the potassium uptake system during fermentation in Saccharomyces cerevisiae.

Fermentable sugars activated the K+ uptake system, increasing the Vmaxs of Rb+, Na+, and Li+ influxes, but sugars did not affect the effluxes of these cations. This activation seems to be a direct effect of fermentation and not the consequence of the H+ pump ATPase activation or internal pH decrease produced by fermentation.

A novel P-type ATPase from yeast involved in sodium transport.

The gene ENA1 was cloned by its ability to complement the Li+ sensitivity of a low Li(+)-efflux strain. The nucleotide sequence of the cloned DNA fragment showed that there are two almost identical genes in tandem, and predicts that they encode P-ATPases. Disruption of both genes originated a strain defective in Na+ and Li+ effluxes, and sensitive to Na+, to Li+ and to alkaline pH. By transformation with ENA1 the defective effluxes and tolerances were repaired.