Aleksandar L. Krunic

Birt–Hogg–Dubé Syndrome

Birt–Hogg–Dubé Syndrome is an autosomal dominant condition characterized by a triad of fibrofolliculomas, trichodiscomas, and acrochordons. Since the first description in 1977, many conditions have been described in association with its clinical triad. Recent epidemiological studies have shown a significant association between the occurrence of lesions in the fibrofolliculoma/trichodiscoma category with renal neoplasms and pneumothoracies. The BHD protein folliculin had recently been identified. The histological findings of the clinical lesions are distinctive. We report a patient with a history of melanoma who presented for routine surveillance. Facial lesions in the fibrofolliculoma/trichodiscoma category were identified. Diagnostic work‐up revealed concomitant multinodular goiter, pulmonary cyst, and renal mass. The patient later developed pneumothorax. Clinical manifestations, histological findings, associations, management, and a review of the Birt–Hogg–Dubé Syndrome are discussed.

Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the CSTA gene encoding cystatin A.

Acral peeling skin syndrome (APSS) is a clinically and genetically heterogeneous disorder. We used whole‐exome sequencing to identify the molecular basis of APSS in a consanguineous Jordanian‐American pedigree. We identified a homozygous nonsense mutation (p.Lys22X) in the CSTA gene, encoding cystatin A, that was confirmed using Sanger sequencing. Cystatin A is a protease inhibitor found in the cornified cell envelope, and loss‐of‐function mutations have previously been reported in two cases of exfoliative ichthyosis. Our study expands the molecular pathology of APSS and demonstrates the value of next‐generation sequencing in the genetic characterization of inherited skin diseases.

Multiple clustered dermatofibroma: case report and review of the literature

The presence of multiple dermatofibromas is rare and is defined as more than 15 lesions. Multiple clustered dermatofibroma (MCDF) is a distinct entity with only 12 reported cases in the literature. MCDF occurs in healthy individuals of both sexes in the first to third decades on the lower half of the body and portends an excellent prognosis. On histology, MCDF is consistent with benign dermatofibromas. We report a 31‐year‐old healthy Hispanic woman with a 14‐year history of slowly progressive MCDF located on her right hip initially misdiagnosed as dermatofibrosarcoma protuberans. We believe this case represents the 13th report of MCDF in the literature and the second from North America.

Signet-ring cell carcinoma of the gallbladder with skin metastases

Cutaneous metastasis from gallbladder cancer is extremely rare. We present a case of signet‐ring cell carcinoma of the gallbladder metastatic to the skin in a 38‐year‐old man. The skin nodules on the face, scalp and perianal area occurred approximately 1 year after the resection of the neoplasm. Skin metastases from gastrointestinal cancers are usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, and rarely present at other sites. Multiple imaging studies revealed the presence of metastatic bony involvement in the spine and left orbit. Visceral metastases have not been demonstrated in our patient in 20 months of follow up since the initial diagnosis of gallbladder cancer was made. We also briefly discuss other primary and metastatic skin tumours with signet‐ring cell morphology.

Multiple Epidermolytic Acanthomas Must Not be Confused with Genital Human Papillomavirus Infection

We describe two patients with multiple epidermolytic acanthomas on the scrotum initially referred to our clinic as genital warts. Both patients presented with multiple tan-colored warty papules scattered on the scrotal skin. Biopsy revealed hyperkeratosis, hypergranulosis, and clear cell changes consistent with epidermolytic acanthoma. Human papillomavirus was not detected and the lesions cleared rapidly with a liquid nitrogen cryoprobe. Despite only a few reports of multiple epidermolytic acanthomas of the scrotum, it may not be as rare as previously thought. In addition, genital localization of the wart-like lesions may lead to confusion with other conditions such as condylomata acuminata, molluscum contagiosum, or bowenoid papulosis.

Subungual and periungual congenital blue naevus

Subungual pigmented lesions should raise concern about malignant melanoma. Blue naevus of the nail apparatus is a rare entity, with only ten cases described in the literature. We report a 21‐year‐old Hispanic woman with a slowly enlarging 1.7 × 2.3‐cm subungual and periungual pigmented plaque present since birth on her right second toe. Initial biopsy was consistent with a blue naevus of the cellular type and, given the recent clinical change and periungual extension, complete excision was recommended. The entire nail unit was resected down to periosteum with prior avulsion of the nail plate. Reconstruction was performed with a full‐thickness skin graft. Follow up at 1 year revealed well‐healed graft and donor sites with complete return of function. We present a case of a congenital subungual and periungual blue naevus of the cellular type and review the literature on this rare presentation of a congenital blue naevus.

Chondrocutaneous advancement flap for reconstruction of helical rim defects in dermatologic surgery

The helical rim is often affected with cutaneous malignancies and requires special attention in the repair, owing to the complex cartilaginous contour, preservation of the aesthetic contour and restoration of its supportive function for eyeglasses and hearing aids. We review the surgical technique of chondrocutaneous advancement flap described by Antia and Buch as one of the most cosmetically appealing and versatile approaches for the repair of small defects of the ear helix.

A Case of Primary Cutaneous Histoplasmosis in a Patient with Diabetes and Multi-Infarct Dementia

We report a case of primary cutaneous histoplasmosis in a fifty‐year‐old African‐American woman with diabetes and multi‐infarct dementia. The patient developed fever and crusted, nodulo‐ulcerative lesions of the skin after accidental superficial trauma to the forehead. The biopsy revealed suppurative granulomatous inflammation with intracellular and extracellular yeast‐like cells with associated clear halo measuring 3–4 μm in size. Systemic involvement was not found. The lesions cleared after treatment with itraconazole 200 mg twice a day for 3 weeks. The medication was continued for a total period of 3 months, with no signs of recurrence after one‐year of follow‐up.

Acral Peeling Skin Syndrome: A Clinically and Genetically Heterogeneous Disorder

Abstract:  Acral peeling skin syndrome (APSS) is a rare, autosomal, recessive genodermatosis characterized by painless spontaneous exfoliation of the skin of the hands and feet at a subcorneal or intracorneal level. It usually presents at birth or appears later in childhood or early adulthood. Some cases result from mutations in the TGM5 gene that encodes transglutaminase 5, which has an important role in cross‐linking cornified cell envelope proteins. We report a new APSS pedigree from Jordan that contains at least 10 affected family members, although sequencing of the TGM5 gene failed to disclose any pathogenic mutation(s). On the basis of probable consanguinity, we performed homozygosity mapping and identified areas of homozygosity on chromosomes 1, 6, 10, 13, and 16, although none of the intervals contained genes of clear relevance to cornification. APSS is a clinically and genetically heterogeneous disorder, and this Jordanian pedigree underscores the likelihood of still further heterogeneity.

The use of antidesmoglein stains in Mohs micrographic surgery. A potential aid for the differentiation of basal cell carcinoma from horizontal sections of the hair follicle and folliculocentric basaloid proliferation.

BACKGROUND Histopathologic differentiation between benign and malignant tissue is of utmost importance for the Mohs surgeon. Folliculocentric basaloid proliferation (FBP) shares many histologic features with basal cell carcinoma (BCC). It is most commonly associated with tumors of areas with abundant hair follicles such as nasal and perinasal skin. Residual BCC incorrectly identified as a horizontally sectioned hair follicle undoubtedly increases the risk of tumor recurrence. Excision of additional layers of normal tissue to remove “funny looking follicles” may have profound impacts on tissue conservation, preservation of function, and cosmesis. Electron microscope studies of BCC revealed a significant reduction of desmosomes compared with normal basal cells and hair follicle keratinocytes. OBJECTIVE This study has assessed the potential of rapid staining with monoclonal antidesmoglein antibody (33‐3D) to discriminate between BCC, horizontally sectioned hair follicles, and FBP. METHODS A rapid immunoperoxidase technique with 33‐3D antidesmoglein antibody was performed on Mohs frozen sections. We selected 18 patients with BCC of nasal and perinasal locations where histologic discrimination between residual tumor and tumor‐free margins with FBP or horizontally sectioned hair follicle was equivocal. RESULTS Fourteen sections disclosed the preservation of desmoglein marker delineating the cell membranes (“perimembranous” pattern) consistent with normal hair follicles. The sections were identified as tumor‐free and no additional stages were performed. The remaining four sections revealed absent perimembranous pattern but presence of diffuse cytoplasmic staining. These were diagnosed as positive for residual BCC requiring the excision of another layer of tissue to obtain tumor‐free margins. A follow‐up period ranging from 6 to 24 months revealed no instance of recurrent disease. CONCLUSION Rapid detection of desmoglein with 33‐3D antibody is a promising tool for discrimination between residual BCC and FBP or horizontally sectioned hair follicles. It may enhance the sensitivity of Mohs surgery by disclosing the hidden foci of BCC, thus preventing tumor recurrence and unnecessary excision of normal tissue.