Ultrasound Morphologic Features of Steatocystoma Multiplex With Clinical Correlation

The ultrasound features of 87 steatocytoma multiplex (SCM) lesions detected in 9 patients are reported. Steatocytoma multiplex is a hamartomatous condition derived from the pilosebaceous duct junction that generates multiple cutaneous cystic lesions. It appeared as clusters of well-defined hypoechoic nodules with mild posterior enhancement in 100% of cases, with both dermal and subcutaneous locations in 67%. No calcification foci were detected within or at the periphery of the lesions. Fifty-six percent of the cases showed signs of hypervascularity in the edge of the nodules, and 44% of the lesions were associated with another dermatologic condition, most frequent being hidradenitis suppurativa (75%), followed by vellus hair cysts (25%). Steatocytoma multiplex shows ultrasound features that allow discrimination from other common cutaneous entities.     

Clinical, dermoscopy and histological correlation study of melanotic pigmentations in excision scars of melanocytic tumours

BACKGROUND: Melanotic pigmentations in scars consecutive to the excision of melanocytic tumours can be secondary to a reactive phenomenon related to the scar tissue or to a recurrence of the melanocytic lesion excised in the first case. Recurrent naevi may sometimes adopt unusual features that make them difficult to differentiate from a melanoma. OBJECTIVES: To describe the clinical, dermoscopic and histological features of melanotic pigmentations in scars consecutive to the excision of melanocytic tumours, and to correlate the histological diagnosis with the dermoscopic features. METHODS: This was a prospective cohort study using macrophotography, dermoscopy and histopathological study. Ninety-five melanotic pigmentations (77 patients) in scars secondary to the excision of melanocytic tumours were prospectively collected in the Department of Dermatology at the Instituto Valenciano de Oncología in Valencia, Spain. Histopathological study was performed in 57 scars. RESULTS: Thirteen dermoscopic structures were identified. Four criteria allowed a differentiation between reactive and specific melanocytic pigmentations. Presence of globules and presence of heterogeneous pigmentation were features associated with specific melanocytic pigmentations (P < 0.0001). Presence of a regular network and presence of streaks were more frequently found in reactive pigmentations (P = 0.023 and 0.026, respectively). CONCLUSIONS: Dermoscopic examination of melanotic pigmentations in excision scars of melanocytic tumours provides useful information about the origin of that pigmentation. Based on such information, recurrent naevi can be differentiated from reactive pigmentations in most cases. Excision and histopathological diagnosis continue to be imperative in some cases of recurrent naevi with atypical clinical features.     

Pseudohermaphroditism due to XY gonadal absence syndrome.

A 21-year-old phenotypic female with a 46,XY chromosome complement and gonadal absence was studied. Basal levels of plasma immunoreactive luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and oestradiol were measured. Pituitary sensitivity and reserve was evaluated by the exogenous administration of synthetic luteinizing hormone-releasing hormone. The episodic release of gonadotrophins was assessed by measuring plasma LH and FSH in plasma samples obtained at 20-minute intervals for a 4-hour period. Endocrine gonadal function was evaluated by a stimulation test with human chorionic gonadotrophin for 3 days. The results showed: a) persistently raised plasma levels of both LH and FSH; b) a pulsatile pattern of release of both gonadotrophins and a normal pituitary response to the synthetic hypothalamic decapeptide; and c) extremely low levels of circulating testosterone and oestradiol with a lack of response to the HCG stimulus. A careful exploratory laparotomy revealed absence of uterus, Fallopian tubes, the Mullerian portion of the vagina, and gonads. No Wolffian derivatives were found. A dissociation of testosterone and the so-called Jost substance effects during early sexual development may explain the findings in this unusual abnormality. The term 'XY gonadal absence syndrome' including five types of variants to designate this condition is proposed.     

Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography

In this study, we have used time-lapse video cinematography to study fertilization in 50 human oocytes that had undergone intracytoplasmic sperm injection (ICSI). Time-lapse recording commenced shortly after ICSI and proceeded for 17-20 h. Oocytes were cultured in an environmental chamber which was maintained under standard culture conditions. Overall, 38 oocytes (76%) were fertilized normally, and the fertilization rate and embryo quality were not significantly different from 487 sibling oocytes cultured in a conventional incubator. Normal fertilization followed a defined course of events, although the timing of these events varied markedly between oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular waves of granulation within the ooplasm which had a periodicity of 20-53 min. The sperm head decondensed during this granulation phase. The second polar body was then extruded, and this was followed by the central formation of the male pronucleus. The female pronucleus formed in the cytoplasm adjacent to the second polar body at the same time as, or slightly after, the male pronucleus, and was subsequently drawn towards the male pronucleus until the two abutted. Both pronuclei then increased in size, the nucleoli moved around within the pronuclei and some nucleoli coalesced. During pronuclear growth, the organelles contracted from the cortex towards the centre of the oocyte, leaving a clear cortical zone. The oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during the course of the observation period. The female pronucleus was significantly smaller in diameter than the male pronucleus (24.1 and 22.4 microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0 respectively, P < 0.0001). After time-lapse recording, oocytes were cultured for 48 h prior to embryo transfer or cryopreservation. Embryo quality was related to fertilization events and periodicity of the cytoplasmic wave, and it was found that good quality embryos arose from oocytes that had more uniform timing from injection to pronuclear abuttal and tended to have a longer cytoplasmic wave. In conclusion, we have shown that time-lapse video cinematography is an excellent tool for studying fertilization and early embryo development, and have demonstrated that human fertilization comprises numerous complex dynamic events.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.