Cutaneous Sweat Gland Carcinomas with Basaloid Differentiation: An Update with Emphasis on Differential Diagnoses.

This article focuses on primary cutaneous sweat gland carcinomas with basaloid differentiation, including cribriform apocrine carcinoma, endocrine mucin-producing sweat gland carcinoma, mucinous carcinoma, adenoid cystic carcinoma, spiradenocarcinoma, and digital papillary adenocarcinoma. These tumors are rare and pose a significant diagnostic challenge. Their clinical presentation is nonspecific and there is significant overlap of their histologic features. Confident diagnosis is necessary because their clinical behavior ranges from indolent, nonrecurring, nonmetastasizing tumors to those with potential for disseminated disease and mortality. They should be separated from cutaneous metastases of primary visceral adenocarcinomas. Salient features of these rare entities are discussed with emphasis on distinguishing features and diagnostic clues.

Sebaceous Neoplasms.

Sebaceous skin tumors are classified into sebaceous adenoma, sebaceoma, and sebaceous carcinoma. An additional group of cystic sebaceous tumors indicate the Muir-Torre syndrome (MTS). Cystic sebaceous tumors are considered as morphologic variants of the 3 main categories. Multilineage adnexal tumors with partly sebaceous differentiation may pose a challenge to categorize. Sebaceous hyperplasia and nevus sebaceus are not considered as true sebaceous tumor entities. Recently, attention has been drawn to morphologic clues of sebaceous differentiation. Immunohistochemistry using the mismatch repair proteins and/or genetic microsatellite instability testing should be performed on sebaceous neoplasms to diagnose MTS as early as possible.

Squared-Off Nuclei and "Appliqué" Pattern as a Histopathological Clue to Periocular Sebaceous Carcinoma: A Clinicopathological Study of 50 Neoplasms From 46 Patients.

The histopathological diagnosis of periocular sebaceous carcinoma can be difficult in poorly differentiated cases showing few mature sebocytes. The authors examined 50 periocular sebaceous carcinomas from 46 patients to determine the frequency of 2 features seen in this neoplasm, namely cells with squared-off nuclei and so-called "appliqué" pattern (peritumoral subnecrosis of peripherally located neoplastic cells). Neoplastic cells with squared-off nuclei were found in varying numbers in both the intraepithelial and dermal (invasive) components in all neoplasms, whereas the appliqué pattern was observed in a third of the cases. It is concluded that these features, taken together, may serve as a clue for the diagnosis of periocular sebaceous carcinoma.

Infundibulocystic Structures and Prominent Squamous Metaplasia in Sebaceoma-A Rare Feature. A Clinicopathologic Study of 10 Cases.

The authors describe 10 cases of sebaceoma that manifested prominent infundibulocystic structures in all cases and, additionally, conspicuous squamous metaplasia in 6 neoplasms. All tumors occurred on the scalp or the face (2 cases lacked clinical information) and presented as a solitary lesion, measuring from 5 to 20 mm. The patients' age ranged from 22 to 89 years. The main component of all tumors was small, uniform basaloid cells (immature sebocytes) intermixed with mature sebocytes clearly arranged in nodules, classifying the lesions as a sebaceoma. In all neoplasms, the tumor cells showed organoid growth patterns of sebaceoma, including rippled, sinusoidal/labyrinthine, and carcinoid-like, occurring alone or in combination. Additionally, numerous infundibulocystic structures were readily noticed and were either distributed multifocally or unilocular within the tumors. In some cases, they were segregated from the main tumor bulk. The authors posit that these structures, which are different from both sebaceous ductal differentiation and squamous metaplasia, represent an authentic follicular differentiation. The infundibulocystic features (combined with squamous metaplasia), when prominent and in a limited biopsy specimen, may cause a confusion with trichoadenoma or even microcystic adnexal carcinoma.

Phacomatosis pigmentokeratotica is caused by a postzygotic HRAS mutation in a multipotent progenitor cell.

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.

Mirror, mirror on the wall: hypercalcemia as a consequence of modern cosmetic treatment with liquid silicone.

BACKGROUND: Hypercalcemia is a common problem in clinical practice and can be related to endocrine disorders or malignant disease, especially in elderly patients. Although rare, other causes can also be responsible. CASE REPORT: Granulomatous inflammation of the skin and lymph nodes induced by intravenous or injectable silicone is a rare condition of hypercalcemia that is usually not within the scope of differential diagnosis. Here, we report a 72-year-old woman with symptomatic hypercalcemia related to cosmetic treatment of the neck. Topical applied liquid silicone by means of a focal ultrasound device induced extensive granulomatous inflammation of the skin and local lymph nodes, being the underlying cause for hypercalcemia in this case. CONCLUSIONS: In rare cases, symptomatic hypercalcemia can be caused by silicone due to a severe granulomatous tissue reaction. This is the first time that a transdermal silicone treatment has been reported to cause severe granulomatous tissue inflammation.

Congenital spindle cell naevus with unusual transformation: proliferative nodule or melanoma?

Congenital melanocytic naevi can give rise to secondary melanocytic tumours, such as proliferative nodules and malignant melanoma. The clinical and histological features of both lesions may be nearly identical, which makes an unequivocal diagnosis impossible. In particular, it is difficult to differentiate clearly between benign and malignant proliferation in infants with secondary melanocytic proliferation. Reports on melanocytic proliferation and malignant melanoma within the paediatric age-group are very rare. There is limited expert knowledge on this subject and little is known about prognosis and outcome. We report here a case of an infant with an unusual transformation of a congenital spindle cell naevus of the umbilical region, and discuss clinical, histological and genomic criteria.

Combined nevus with dermally located pagetoid cells in the perianal region: a new variant of site-related histological atypia.

Nevi with site-related histological atypia have been reported in various locations, mainly on the female genitalia, along the anatomical milk line and in skin folds. Therefore, the literature focuses clearly on the atypical nevi of the female genitalia. In the present case, we describe a unique case of a combined perianal melanocytic nevus with architectural and cytologic atypia that differ from the histopathologic features of accepted criteria for atypical genital nevi. A suspicion of malignant melanoma was raised, but few pivotal histological features, the age of the patient and the clinical follow-up for 10 years proved otherwise. This case contributes to the collection of necessary information about perianal nevi that show obvious variations in site-related histological atypia compared with atypical genital nevi. Although the malignant potential of such lesions remains unclear, it is important to prevent overdiagnosis of malignant melanoma with the associated devastating surgery, especially in young patients.

Meyerson-Phenomenon hides a nevus flammeus.

Facial eczema is a common disease in daily dermatological practice. The cause of facial eczema is often atopic dermatitis or allergic contact dermatitis. Usually, the eczema resolves with correct topical treatment and by avoiding allergic trigger factors. A 49-year-old woman presented with persistent eczema on her forehead which recurred over decades despite correct topical therapy. A skin biopsy revealed the astonishing diagnosis of a nevus flammeus with an overlying eczema known as the Meyerson phenomenon. The Meyerson phenomenon is often described in children with nevi flammei suffering from atopic dermatitis - in adults the phenomenon is rarely recognized as a reason for eczema. We show the interesting case of an adult woman with the Meyerson phenomenon on a nevus flammeus and discuss the possible pathomechanisms.

Blaschkitis in children - a new entity?

Blaschkitis is an acquired, rare dermatitis that follows the lines of Blaschko. Many consider blaschkitis as a variant of lichen striatus, although authors felt that it is a separate entity. A 2½-year-old girl presented with multiple grouped papules along the lines of Blaschko on her trunk. The main differences to lichen striatus are illustrated. Our case supports the hypothesis that blaschkitis is an entity of its own.