Victor Desmond Mandel

Acne: in vivo morphologic study of lesions and surrounding skin by means of reflectance confocal microscopy

Acne vulgaris is a common disease of the pilosebaceous unit, clinically showing alteration of the keratinization process leading to comedos formation and subsequent inflammatory process.

Congenital “self-healing” Langerhans cell histiocytosis (Hashimoto-Pritzker disease): A report of two cases with the same cutaneous manifestations but different clinical course

Congenital self‐healing Langerhans cell histiocytosis or Hashimoto‐Pritzker disease is a rare condition present at birth or in the neonatal period characterized by small reddish‐brown crusted papulonodular lesions. In most cases these lesions are not accompanied by systemic findings and tend to involute spontaneously within weeks or months, but in other cases there may be extracutaneous involvement and/or recurrence of the disease. This emphasizes that the clinical course is variable and a long‐term follow‐up is mandatory in order to reveal possible systemic involvement. We describe two cases of congenital self‐healing Langerhans cell histiocytosis with widespread and very similar cutaneous manifestations but different clinical course. The first patient had multisystemic disease (with lymph nodes, bones, liver and lungs affected) that required systemic therapy. The second patient had cutaneous and bony lesions that resolved spontaneously. We think that the adjective “self‐healing” is misleading and should be abandoned. We stress the importance of a complete systemic evaluation and the necessity of a long‐term follow‐up.

Pemphigus with features of both vulgaris and foliaceus variants localized to the nose

We report the case of a 74‐year‐old man affected by an unusual variant of pemphigus. He presented with a crusty and scaly lesion of the nose. We performed reflectance confocal microscopy and optical coherence tomography on the lesion, which suggested an unexpected diagnosis of pemphigus. Therefore, to confirm our diagnostic suspicions, we executed indirect immunofluorescence and two biopsies, one for histopathological examination and one for direct immunofluorescence. Histopathological evaluation showed acantholysis with formation of clefts in the granular and spinous layers of the epidermis. Direct immunofluorescence revealed immunoglobulin G and C3 deposit to the full thickness of the epidermis. Indirect immunofluorescence showed intercellular antibodies at a titer of 1:40 in the suprabasal epidermis. The immunoblot analysis using epidermal extract revealed the presence of circulating antibodies directed to 130‐ and 160‐kDa antigens in the patients serum. These two antigens were evidenced from nitrocellulose membrane with colorimetric AP systems, which highlighted the presence of autoantibodies against desmoglein (Dsg)1 and Dsg3 (sodium dodecylsulfate polyacrylamide gel electrophoresis). We also performed an enzyme‐linked immunoassay. All these findings suggested that this patients pemphigus had features of both vulgaris and foliaceus variants.

Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi

BackgroundGlioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature.Case presentationWe describe the case of a patient with congenital GBM who developed eruptive disseminated Spitz nevi (EDSN) after chemotherapy. Few cases of EDSN have been described in literature and this rare clinical variant, which occurs predominantly in adults, is characterized by multiple Spitz nevi in the trunk, buttocks, elbows and knees. There is no satisfactory treatment for EDSN and the best therapeutic choice is considered the clinical observation of melanocytic lesions.ConclusionWe recommend a close follow-up of these patients with clinical observation, dermoscopy and reflectance confocal microscopy (RCM). However, we suggest a surgical excision of the lesions suspected of being malignant.

Acne: morphologic and vascular study of lesions and surrounding skin by means of optical coherence tomography

Acne vulgaris is a disease of the pilosebaceous unit, characterized by hyper‐keratinization process, comedos formation and inflammatory reactions.

Confocal microscopy characterization of BRAFV600E mutated melanomas.

Thanks to modern techniques, molecular signatures for melanoma are now identifiable and have opened new horizons in the treatment of metastatic disease with molecular-targeted therapies. We distinguish different melanoma subtypes on the basis of genetic mutations such as BRAFV600E and we can therefore hypothesize the existence of corresponding morphological patterns that might be detected in vivo by noninvasive diagnostic tools such as dermoscopy and confocal microscopy. Eight BRAFV600E mutated melanomas (six primary and two metastases) were collected, matched in terms of age, sex, and thickness wild-type controls, and analyzed. In this preliminary study, regression, corresponding to fibrosis and melanophages in the dermis, was the predominant pattern and was also observed confocally when dermoscopy showed no peppering. In particular, confocal microscopy could not only detect regression but also provided a semiquantitative analysis of its grade through the count of melanophages. Confocal microscopy can be proposed as a useful tool in the preliminary screening and characterization of BRAFV600E mutated melanomas, providing new insights for patients’ screening and follow-up.

Multiple primary melanomas versus single melanoma of the head and neck: a comparison of genetic, diagnostic, and therapeutic implications.

Single primary and multiple primary melanomas (MPMs) of the head and neck region may be confused at first glance because of the common clinical and dermoscopic patterns. An inaccurate diagnosis may lead the clinician to a wrong diagnostic and therapeutic pathway because MPMs occurring in familial or sporadic settings are often involved in individual cancer susceptibility. We investigated the clinical, demographic, histological, and survival differences between MPMs and single melanoma occurring in the head and neck region. A retrospective analysis of medical and histologic records from 217 melanomas of the head and neck region was carried out. Malignant neoplasms affecting MPMs patients were also reported. Mutational analysis of specific genes was carried out when clinical data and family history were suggestive for a familial/hereditary setting. Two hundred and five out of 217 (94.5%) patients were affected by single primary melanoma and 12 (5.5%) by MPMs of the head and neck region. Individuals affected by MPMs were distinguished by a significantly higher mutation frequency and a higher prevalence of malignant neoplasms such as renal cancer. Genetic testing showed germline mutations affecting MITF E318K, CDKN2A genes. Our data highlight the importance of strict cancer surveillance in individuals with MPMs and the role of appropriate genetic counseling and testing in selected patients. Finally, personalized clinical and instrumental screening and follow-up strategies should also be based on mutational status. A heightened level of suspicion is required in the clinical management of mutation carriers.

Hypomelanosis of Ito with a trisomy 2 mosaicism: a case report

IntroductionHypomelanosis of Ito is a rare neurocutaneous disorder, characterized by streaks and swirls of hypopigmentation following the lines of Blaschko that may be associated to systemic abnormalities involving the central nervous system and musculoskeletal system. Despite the preponderance of reported sporadic hypomelanosis of Ito, few reports of familial hypomelanosis of Ito have been described.Case presentationA 6-month-old Caucasian girl presented with unilateral areas of hypomelanosis distributed on the left half of her body and her father presented with similar mosaic hypopigmented lesions on his upper chest. Whereas both blood karyotypes obtained from peripheral lymphocyte cultures were normal, a 16% trisomy 2 mosaicism was found in cultured skinfibroblasts derived from a hypopigmented skin area of her father.ConclusionsFamilial cases of hypomelanosis of Ito are very rare and can occur in patients without systemic involvement. Hypomelanosis of Ito constitutes a non-specific diagnostic definition including different clinical entities with a wide phenotypic variability, either sporadic or familial. Unfortunately, a large number of cases remain misdiagnosed due to both diagnostic challenges and controversial issues on cutaneous biopsies in the pediatric population.

Skeletal and cranio-facial signs in Gorlin syndrome from ancient Egypt to the modern age: sphenoid asymmetry in a patient with a novel PTCH1 mutation.

Gorlin syndrome is an autosomal dominant disorder linked to PTCH1 mutation, identified by a collection of clinical and radiologic signs. We describe the case of a family in which father and son fulfilled clear cut diagnostic criteria for Gorlin syndrome including multiple basal cell carcinomas, keratocystic odontogenic tumors, atypical skeletal anomalies and a novel PTCH1 germline mutation (c.1041delAA). Craniofacial and other skeletal anomalies displayed at 3D and helical CT scan were: macrocephaly, positional plagiocephaly, skull base and sphenoid asymmetry, bifidity of multiple ribs and giant multilocular odontogenic jaw cysts. Extensive multilamellar calcifications were found in falx cerebri, tentorium, falx cerebelli and in the atlanto-occipital ligament. The inclusion of bifid ribs as a novel major criteri may be useful for the recognition and characterization of misdiagnosed cases.

Diagnostic and pathogenetic role of café-au-lait macules in nevoid basal cell carcinoma syndrome

Café au lait spots (CALS) are common dermatologic findings that can at the same time arise in a variety of pathologic conditions such as Neurofibromatosis type 1 (NF1), together with numerous hereditary syndromes for which they represent either diagnostic criteria or associated elements (McCune Albright, Silver-Russell, LEOPARD, Ataxia-Telangiectasia). A review of the literature also revealed two cases of association with NBCCS. We report here the case of a female proband with CALS associated to Nevoid Basal Cell Carcinoma Syndrome (NBCCS) with known PTCH1 germline mutation (C.1348-2A>G) who had been misdiagnosed with NF1 in her childhood because of 5 CALS and cutaneous nodules. The patient presented a giant cell tumor of the skin, palmar and calcaneal epidermoidal cystic nodules, odontogenic keratocystic tumors and deformity of the jaw profile. Her family history brought both her brother and father to our attention because of the presence of KCOTs diagnosed at early age: after genetic testing, the same PTCH1 germline mutation was identified in the three family members. Clinical criteria are used for discerning NF1 diagnosis (size, number and onset age), while there are no definite guidelines concerning CALS except for their presence. In our experience, we have noted an association of CALS with NBCCS; this seems interesting because we already know clinical criteria are a dynamic entity and can be modified by epidemiologic evidences.