Authors: Rebecca M Gerlach, Mark A Chaney

PubMed: 34317720
DOI: 10.1016/j.xjtc.2020.01.011

Review

Authors: Ricardo Correa, Paraskevi Salpea, Constantine A Stratakis...

Carney complex (CNC) is a rare autosomal dominant syndrome, characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas and multiple endocrine tumors. The disease is caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22-24 coding for the regulatory subunit type I alpha of protein kinase A (PKA) gene. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). In this report, we review CNC, its clinical features, diagnosis, treatment and molecular etiology, including PRKAR1A mutations and the newest on PRKACA and PRKACB defects especially as they pertain to adrenal tumors and Cushing's syndrome.

Topics: Carney Complex; Cushing Syndrome; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Humans; Mutation

PubMed: 26130139
DOI: 10.1530/EJE-15-0209

Authors: Young Bin Lee, Won-Soo Lee

PubMed: 34858016
DOI: 10.5021/ad.2021.33.6.591

Authors: Ken Iida, Takeshi Egi, Masato Shigi...

Cutaneous myxoma is a rare neoplasm typically occurring as an asymptomatic nodule on the head, neck, and chest regions of adults. However, multiple cutaneous myxoma of the subungual space is even rarer. Here, we report a case of multiple cutaneous myxoma of the subungual space in which the tumor was removed by creating a mid-radial incision while preserving the nail matrix. The excisional biopsy samples were dispatched for histopathological examination and confirmed to be cutaneous myxoma. To the best of our knowledge, this is the first report on multiple cutaneous myxoma of the subungual space.

PubMed: 30881822
DOI: 10.1097/GOX.0000000000002040

Review

Authors: Peter J Kerr, June Liu, Isabella Cattadori...

Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit (Oryctolagus cuniculus), MYXV causes the lethal disease myxomatosis. The release of MYXV as a biological control for the wild European rabbit population in Australia, initiated one of the great experiments in evolution. The subsequent coevolution of MYXV and rabbits is a classic example of natural selection acting on virulence as a pathogen adapts to a novel host species. Slightly attenuated mutants of the progenitor virus were more readily transmitted by the mosquito vector because the infected rabbit survived longer, while highly attenuated viruses could be controlled by the rabbit immune response. As a consequence, moderately attenuated viruses came to dominate. This evolution of the virus was accompanied by selection for genetic resistance in the wild rabbit population, which may have created an ongoing co-evolutionary dynamic between resistance and virulence for efficient transmission. This natural experiment was repeated on a continental scale with the release of a separate strain of MYXV in France and its subsequent spread throughout Europe. The selection of attenuated strains of virus and resistant rabbits mirrored the experience in Australia in a very different environment, albeit with somewhat different rates. Genome sequencing of the progenitor virus and the early radiation, as well as those from the 1990s in Australia and Europe, has shown that although MYXV evolved at high rates there was no conserved route to attenuation or back to virulence. In contrast, it seems that these relatively large viral genomes have the flexibility for multiple pathways that converge on a similar phenotype.

Topics: Adaptation, Biological; Animals; Australia; Biological Evolution; France; Genotype; Myxoma virus; Myxomatosis, Infectious; Rabbits; Virulence

PubMed: 25757062
DOI: 10.3390/v7031020

Authors: Jordan R Yaron, Liqiang Zhang, Qiuyun Guo...

Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or "fine tune" the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.

PubMed: 33105865
DOI: 10.3390/pharmaceutics12111003

Authors: Mina M Naguib, Caroline Craven, Alan Kozarsky...

Neurothekeomas (NTKs) are benign cutaneous neoplasms of fibrohistiocytic origin and most commonly occur in the head, neck, and upper extremities. Traditionally, NTK and nerve sheath myxoma (NSM) were classified as subtypes of a single neoplasm with a common histogenesis, but recently immunostaining has demonstrated that the lesions are most likely of distinct cellular origin. Rarely, NTKs have been reported to occur in the ocular adnexa, and the present case of a 39-year-old female is the first to describe a cellular NTK originating in the cornea and mimicking a Salzmann's nodular degeneration. This report describes the clinical and pathological findings of the patient, discusses the changes in the classification of these rare neoplasms in light of advances in immunohistochemistry, and reviews all cases of ocular NTK found in the literature.

PubMed: 27843897
DOI: 10.1159/000444716

Authors: Wei Wan, Liang Zeng, Hongqun Jiang...

Mutations in PRKAR1A gene can lead to Carney complex (CNC), and most CNC patients develop cardiac and cutaneous myxomas. In particular, cardiac myxomas are a common cause of mortality in CNC patients. Cutaneous myxomas of the external ear are extremely rare, and do not have any specific clinical features In this retrospective study, we analyzed the clinical and genetic data of the proband and his family and fifty whole blood control samples selected from the molecular genetic database of our hospital. Whole exome DNA sequencing analysis was used to detect the mutation in the peripheral blood samples. The results of the clinical analysis showed the presence of spotty skin pigmentation and external auditory canal myxoma in the proband as well as in his sister and mother. Whole-exome DNA sequencing showed a novel heterozygous mutation in the PRKAR1A gene i.e., c.824_825delAG (p.Gln275Leufs*2), in the proband and his sister and mother. In conclusion, the family members had the same autosomal dominant PRKAR1A mutation. DNA sequencing revealed a novel c.824_825delAG in exon 9 of PRKAR1A. This pathogenic mutation has not been reported previously, and may be related to the occurrence of external auditory canal myxomas and spotty pigmentation. This study broadens the genotypic spectrum of PRKAR1A mutations in CNC.

PubMed: 36092889
DOI: 10.3389/fgene.2022.947305

Review

Authors: Florica Sandru, Mihai Cristian Dumitrascu, Aida Petca...

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumors with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.

PubMed: 34630667
DOI: 10.3892/etm.2021.10748