Calcinosis cutis following contact with calcium chloride solution.

Calcinosis cutis is the deposition of insoluble calcium in the cutaneous tissue. Calcinosis cutis can be classified as metastatic, dystrophic, idiopathic or exogenous. We report a 48-year-old white man who was dismantling a portable ice skating rink when calcium chloride solution from the pipes spilt onto his clothing. Several days later, he started to develop mildly pruritic erythematous papules, some studded with white deposits and some with umbilication over the exposed areas corresponding to the spillage of the calcium chloride solution. Histological features revealed interstitial fibrohistiocytic reaction with calcium-encrusted degenerated collagen bundles in the dermis which was further confirmed by von Kossa stain. He was commenced on topical corticosteroid cream twice daily and the lesions cleared completely between 6 to 10 weeks.

The syndrome of hereditary leiomyomatosis and renal cell cancer (HLRCC): The clinical features of an individual with a fumarate hydratase gene mutation.

A 55-year-old woman presented with multiple cutaneous leiomyomas and multiple uterine leiomyomas (fibroids). The clinical diagnosis of the autosomal dominant hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome was confirmed by identification of a fumarate hydratase gene mutation. This case highlights the need to consider the possibility of renal and uterine cancer in members of cutaneous leiomyomatosis families.

Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice.

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1alpha of protein kinase A) mutations in CNC. Mutational analyses of the PRKAR1A gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to PRKAR1A haploinsufficiency. Therefore, we studied the consequences of prkar1a haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in prkar1a(+/-) mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover, prkar1a(+/-) mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from prkar1a(+/-) mice did not exhibit prkar1a loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation.

Versatile and facile synthesis of diverse semisynthetic tetracycline derivatives via Pd-catalyzed reactions.

A diverse collection of tetracycline derivatives has been synthesized utilizing Heck, Suzuki, and other palladium-coupling reactions via tetracycline arenediazonium and iodoarene salts. Large numbers of tetracyclines are now possible via these reactions, including numerous upper periphery derivatives of doxycycline, minocycline, sancycline, and methacycline modified at positions C7, C9, and C6-C13 on the tetracycline naphthacene ring. Application of palladium-coupling reactions to the tetracyclines has yielded new tetracycline classes with differing structural attributes, greatly increasing the structural diversity of this family of antibiotics, one of the last of the early antibiotic families to be expanded by organic and medicinal chemistry.

Genetic testing of the family with a Carney-complex member leads to successful early removal of an asymptomatic atrial myxoma in the mother of the patient.

Carney complex is a rare cardiocutaneous syndrome with an autosomal-dominant inheritance pattern. Apart from its cutaneous manifestations of multiple blue naevi and lentigines, it can involve multiple other organ systems, particularly the heart, where myxoma tumours commonly develop and can potentially lead to serious complications such as cerebrovascular accidents and myocardial infarction. Recently, a specific mutation in the gene encoding the R1-alpha regulatory subunit of cyclic adenosine monophosphate-dependent protein kinase A (PRKAR1alpha) has been discovered and found to be associated with a high risk of developing cardiac myxomas. We report the case of a Carney-complex family member who displayed no observable clinical or cardiac features of the disease but who was found to be positive for the PRKAR1alpha gene mutation on genetic testing. Further evaluation of this patient subsequently led to the discovery of a 3-cm atrial myxoma that had previously been undetected on cardiac assessment. This case highlights the potential benefits of using genetic screening for this disease.

Stage IV CD30+ anaplastic large cell lymphoma: response to acitretin and interferon-alpha.

Retinoids and interferon (IFN)-alpha induce differentiation, affect cell proliferation and alter various immune parameters. In combination, their effects may be additive or even synergistic in the treatment of malignancy. We present a 53-year-old woman with stage IV CD30+ anaplastic large cell lymphoma with brain, lung and skin involvement. The patient had been on methotrexate for rheumatoid arthritis. After a combination of oral acitretin 50 mg daily and IFN-alpha 3 million units subcutaneously 3 times per week, the skin lesions cleared within 2 months, lung lesions by 5 months and brain lesions by 7 months. Although we cannot exclude that methotrexate played a role in the development of this lymphoma and that its withdrawal contributed to the clearance of lesions, we propose that the patient's disease responded to the combination of acitretin and IFN-alpha.