Multiple hereditary infundibulocystic basal cell carcinomas: a distinctive genodermatosis

Abstract

and P < 0AE001, respectively). The comparison between SJS/TEN and EM did not show a statistical difference, although the mean value of sCD40L was higher in the former.Our results show that in SJS/TEN there is not only an intralesional involvement, but also a systemic activation of the CD40/CD40L system. In particular, the penetration and the diffusion of the triggering agent in genetically predisposed individuals may induce CD4+ T lymphocytes to release sCD40L. Thus, sCD40L may exert its immunological functions by interacting both with circulating CD40+ cells, amplifying the immune response to the whole mucocutaneous surface, and with immune and nonimmune CD40+ cells localized in tissue, contributing to the development of the lesions.Although our study suggests a role for sCD40L as a marker of activation in SJS/TEN, it was not possible to evaluate whether its serum concentrations reflect disease severity. Nevertheless, our data showed that the patients with wider dermalepidermal detachment had the highest levels of sCD40L.Furthermore, our results show that sCD40L was expressed to a greater degree in patients with EM than in controls. This finding suggests that this molecule could be considered a marker of activation also in EM, in which environmental agents, in particular viruses and other microorganisms, may induce a dysregulation of systemic immunity.Finally, possible implications regarding the therapy of SJS/ TEN arise from the present study. Because of the severity of the disease and the high mortality rates of SJS/TEN, new therapeutic agents may be researched. CD40/CD40L interactions are thought to play an important role in the pathogenesis of certain diseases, such as systemic lupus erythematosus (SLE), 6 rheumatoid arthritis 7 and systemic sclerosis. 8 Recently, pharmacological manipulation of this axis has been tried, with promising results both in animal models and in human SLE. 9,10 Although further studies are required, our finding that serum sCD40L concentrations and CD40L+ lesional cells 4 in patients with SJS/TEN are elevated suggests that inhibition of CD40/CD40L interactions could be a therapeutic target in SJS/TEN.

Hedgehog Pathway Alterations Downstream of Patched-1 Are Common in Infundibulocystic Basal Cell Carcinoma

“…For example, keratocystic odontogenic tumor, palmoplantar pitting, and bony abnormalities, all common in NBCCS, have not yet been described in MHIBCC. [12][13][14]22 Conversely, meningioma, which is not a criterion for NBCCS, was seen in one of the MHIBCC patients, 14 which is intriguing because SUFU mutations have been independently associated with meningioma. 29 On the other hand, although NBCCS is overwhelmingly linked to PTCH1 mutations, rare patients that have met clinical criteria for NBCCS have had SUFU mutations.…”

“…Furthermore, although the causative mutation was not identified at that time, linkage analysis suggested that the inherited mutation was unlikely to affect PTCH1, leading the authors to conclude that MHIBCC might represent a novel genodermatosis. 12 Although additional kindreds were subsequently identified, 13 it was not until 2016 that genetic analysis of a MHIBCC patient revealed a SUFU mutation. 14 A second previously identified kindred with a SUFU mutation may also represent MHIBCC.…”

Cytokeratin expression patterns in multiple infundibulocystic basal cell carcinoma

“…IBCC usually represents a solitary lesion and multiple tumors are rare. To our knowledge, there have been five reports of such cases, two of which reported three pedigrees in sum total of multiple hereditary IBCC 10,11 . The other three reports are of multiple IBCC, either located on the face of a person infected with the human immunodeficiency virus, 12 around the mouth with a unilateral presentation, 13 or over the lines of Blaschko 14 …”

A new non‐syndromic type of familial carcinomas?

“…The delineation of these familial cancer syndromes, in particular Gorlin syndrome, has so far overshadowed the possibility that a hereditary non‐syndromic type of tumour may also exist 5,6 . The postulated separate phenotype is characterized by the absence of nevoid lesions.…”