Pigmented epithelioid melanocytoma: report of first Japanese cases previously diagnosed as cellular blue nevus

Background:  The term 'pigmented epithelioid melanocytoma (PEM)' was recently used for borderline melanocytic tumor/low-grade melanoma including cases previously diagnosed as human animal-type melanoma and epithelioid blue nevus. No Japanese cases have been reported.
Methods:  We reviewed 219 cases previously diagnosed as blue nevus in Japan. Common blue nevus was identified in 154 cases and cellular blue nevus in 65 cases.
Results:  We have found two Japanese cases of PEM previously diagnosed as cellular blue nevus. Two patients were female. The age at presentation was 32 and 28 years. Two lesions were on the buttock. Two cases fulfilled histological criteria proposed for PEM. There is no evidence of recurrence or metastases.
Conclusions:  PEM is a distinct melanocytic tumor and the unifying diagnostic term. PEM is present in Japanese, but these cases may be previously diagnosed as cellular blue nevus. Japanese pathologists should recognize a new concept of PEM, and when they make a diagnosis of PEM, they should be recommended sentinel lymph node sampling.     

Occurrence of melanoma in "dysplastic" nevus spilus: report of case and analysis by flow cytometry

We report a case of melanoma arising in a large nevus spilus. On histologic examination, the nevus spilus had diagnostic features of melanocytic dysplasia. Further characterization by flow cytometry showed DNA-aneuploidy within the melanoma as well as in one of the darker pigmented papules within the nevus spilus. The significance of this finding and a review of melanomas originating in nevi spili are presented.     

Cutaneous necrotizing venulitis: a sequential analysis of the morphological alterations occurring after mast cell degranulation in a patient with a unique syndrome

An unusual patient, with dermal nodules, flexion contractures of the fingers and toes, cold-induced urticaria, dermographism and serum hypocomplementaemia, had necrotizing cutaneous venulitis underlying the spontaneous lesions. Since necrotizing cutaneous venulitis could be experimentally induced by the physical stimuli of cold or trauma, the time-course of histopathological events was documented in the skin of this patient. The histopathological alterations were studied in 1 micron thick, Epon-embedded skin biopsy specimens over an interval of 6 days. The early massive degranulation of the mast cells was followed by the sequential infiltration of neutrophilic, eosinophilic and basophilic polymorphonuclear leucocytes, by the development of venular endothelial cell necrosis and by the deposition of fibrin. The persistent serum hypocomplementaemia involved the classic activating and amplification pathways. It seems possible that the unusual combination of pathobiological processes involving the mast cells and the complement system in this patient has created a unique syndrome, in which venules are damaged and the sheaths of the extensor tendons of the hands and feet become affected in time.     

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.      

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.