A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome.

CLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (PIK3CA-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the PIK3CA gene. As an upstream regulator of the PI3K/AKT/mTOR signal transduction pathway, activating mutations of PIK3CA gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term 'CLOVES' is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the PI3K/AKT/mTOR signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.

Primary Cutaneous Angiosarcoma of the Scalp with Cranial Invasion in a Patient with Metastatic Breast Cancer.

Idiopathic cutaneous angiosarcoma (CA) of the head and neck is a distinct subtype of angiosarcoma most commonly presenting as a single or multiple purple, bruise-like patches that arise de novo and enlarge over several months. In clinical practice, both misdiagnosis and delayed diagnosis are frequently encountered. Here, we present a case of idiopathic CA on the scalp with invasion to the cranium in a patient with breast cancer metastatic to the brain. The patient was initially misdiagnosed and mistreated with herpes zoster and breast cancer metastatic to the skin, which led to a delayed diagnosis by two months until dermatologic evaluation. The diagnosis was then firmly established as CA based on consistent clinical and histological features. Since the tumor was inoperable, radiotherapy and chemotherapy were been considered as the appropriate adjuvant modes of therapy. Despite an initial favorable response, the disease demonstrated a rapidly progressive course and the patient succumbed to the disease within six months. This report briefly reviews the clinical and histological portrait and management options for this aggressive tumor.

Demographic, clinical and dermoscopic features of melanocytic nevi on the scalp.

BACKGROUND: The scalp is a special anatomical area and dermoscopic findings of this region may significantly differ from other body parts. OBJECTIVE: To investigate and compare the clinical and dermoscopic patterns of scalp melanocytic nevi in patients ≤15 years of age and above, and to analyse their relevance to demographic features, atypical mole syndrome (AMS) and total body nevus count (TBNC). METHODS: In this retrospective cohort study, the clinical data and dermoscopic images of patients with scalp melanocytic nevi were retrieved, reviewed and analysed. Demographic, clinical and dermoscopic features were compared in patients ≤15 years of age and above. RESULTS: A total of 196 scalp melanocytic nevi in 126 patients (female/male:64/62; ≤15/>15 years of age: 49/77) with a median age of 18.5 years (range 0-72) were evaluated. Statistically, the globular pattern was significantly higher in all age groups, and the papillomatous pattern was significantly lower in patients ≤15 years of age (P = 0.008 and P = 0.005, respectively). The eclipse pattern was significantly higher, and the homogenous pattern was significantly lower in patients ≤15 years of age with AMS (P = 0.003 and P = 0.014, respectively). Finally, patients ≤15 years of age with 50 to 100 TBNC had a higher eclipse pattern than those with 0 to 25 TBNC. CONCLUSION: The findings of this retrospective study might implicate that children with eclipse pattern of scalp melanocytic nevi might be 'moley' in the future with an impending risk of AMS. This hypothesis requires confirmation in future prospective studies on a larger cohort of patients.

Livedoid cutaneous metastasis of signet-ring cell gastric carcinoma.

Cutaneous metastasis of gastric cancer is extremely rare. Nodular forms are more common and inflammatory forms are exceptionally encountered. Herein, we report a case of inflammatory cutaneous metastasis of signet-ring cell gastric cancer (poorly cohesive gastric carcinoma with signet-ring cell component) masquerading as livedo reticularis. To our knowledge, such a clinical presentation of cutaneous metastasis has not been reported for gastric cancer. It is imperative to preserve a high index of clinical suspicion for diagnosing cutaneous metastases. Our case highlights the importance of obtaining a skin biopsy in patients with a known history of internal malignancy. Bizarre, newly erupting, evolving, persistent, or treatment-refractory dermatologic lesions (such as nodules, ulcers, erythematous, reticular, or livedoid patches) might be clues for an underlying internal malignancy and require prompt histopathological sampling. Personal medical history, histopathological examination, and immunohistochemical profiling are equally important in distinguishing primary cutaneous carcinomas from secondary metastatic deposits. Early recognition of a cutaneous metastasis might enable appropriate staging and timely intervention, thereby prolonging survival.

Meyerson Phenomenon as a Component of Melanoma in situ.

Meyerson phenomenon (MP) is characterized by a symmetrical area of erythema and scales encircling a central lesion, which is most commonly a banal melanocytic nevus. Herein, we describe an unusual case with MP representing an eczematized response to a melanoma in situ and review the literature covering this entity. A 56-year-old man presented with a 6-month history of a pruritic, pigmented lesion on the trunk. The patient had no other significant medical history and no notable family history of similar lesions. Physical examination revealed an irregular, hyperpigmented plaque, 1 cm in diameter, with a surrounding halo of erythematous, scaly areas on the right abdominal region (Figure 1, a). On dermatoscopical examination, an irregular, broadened pigment network, radial streaming, and a focal blue-white veil, encircled by a homogenous, erythematous zone was observed (Figure 1, b). Based on clinical and dermatoscopical findings, a presumptive diagnosis of MP occurring on an early melanoma was made and the lesion was excised with a 5 mm safety margin. Histopathological examination of the excised material revealed a central intraepidermal atypical, confluent melanocytic proliferation with angular, hyperkeratotic, and irregular nuclei and a prominent fixation artifact around the cells (Figure 1, c). Human melanoma black (HMB-45) immunostaining highlighted the confluence of the neoplastic melanocytic proliferation. Lymphohistiocytic infiltration with melanophages was also identified in the upper dermis. An interesting feature was the presence of subacute spongiotic dermatitis around the melanocytic lesions (i.e. parakeratosis, serum/crusting, spongiosis, lymphocyte exocytosis, and acanthosis). Immunohistochemical staining with the Langerhans cell marker, CD1a, revealed an increased cell population in the perilesional, erythematous halo (Figure 1, d). A diagnosis of MP existing on melanoma in situ was established with clinical and histopathological findings. No recurrence of the eczematized components or melanocytic lesions was identified despite 1-year follow-up. Also called halo dermatitis and halo eczema, MP presents as an eczematized, perilesional plaque around various lesions, mainly of banal melanocytic nevi (1). Occurrence of halo dermatitis around a melanocytic nevus was first described by Meyerson in 1971. Other cutaneous disorders with MP include those of dysplastic nevus, melanoma, seborrheic keratosis, stucco keratosis, nevus sebaceous, dermatofibroma, vascular malformations, nevus flammeus, molluscum contagiosum, basal cell carcinoma, squamous cell carcinoma, and keloid formation (2-7). History of atopy and atopic dermatitis is observed in a subset of patients, which was absent in our case. Rarely, patients with Behçet's disease, severe sunburn, and cessation of interferon therapy have also been associated with this entity. MP is described to be more frequent in young males and has a tendency to occur in summer. As far as we are aware, there are only two cases of melanoma with features of MP in the literature. Rodin et al. presented a case report showing features of MP around a melanoma in situ arising on a dysplastic nevus (8). By way of comparison, a pre-existing precursor dysplastic nevus was not identified in our case. Dermatoscopic features including scar-like depigmentation and negative pigment network also differed from our case which featured a broadened pigment network, radial streaming, and blue-white veil. The other case report was of a 50-year-old man, presenting with an atypical melanocytic lesion several years in duration showing an erythematous halo (9). Histopathological examination was consistent with a Clark level 2 superficial spreading melanoma, which was cured with excision with no recurrence despite long-term follow-up. As far as we are aware, our case report is the first to describe de novo melanoma in situ without dermal invasion or a precursor dysplastic nevus. The etiopathology of MP is unclear; however it is considered to be immune-mediated. Up-regulation of intercellular adhesion molecule-1 on keratinocytes and dermal endothelial cell surfaces has been shown, suggesting the involvement of adhesion molecules in pathogenesis (10). We hypothesize that increased Langerhans cell population, as observed in our case, results in a delayed immune response reminiscent of an eczematous process in MP. Excision of the central lesion has been reported to precipitate the resolution of dermatitis, as in our case, in which recurrence of the erythematous, scaly eruption was not observed after removal of the central lesion despite a 1-year follow-up period. Some authors recommend pre-treatment of the lesion with topical corticosteroids to suppress the eczematous process in the adjacent skin. Coexistence of MP around a melanocytic nevus (Meyerson nevus) with halo nevus and progression of Meyerson nevus to halo nevus has also been reported. We suggest that melanoma may occur as a component of MP, and careful dermatoscopic examination is essential to differentiate between pigmented lesions with a perilesional erythematous halo.

Pigmented Bowen's disease of the genitalia masquerading as malignant melanoma.

Pigmented Bowen's disease is a rare subtype of in situ squamous cell carcinoma of the skin and mucosa, with a potential risk of invasion and metastasis. It is universally accepted that human papillomavirus (HPV) is the cause of genital Bowen's disease. Herein we report an unusual case of pigmented Bowen's disease of the genital area that clinically simulated malignant melanoma. Accurate diagnosis could only be established after histological examination. Polymerase chain reaction (PCR) analysis showed that the lesion harbored HPV 16 DNA. Although pigmented Bowen's disease is rare, it should be considered in the differential diagnosis of all pigmented lesions of the genitalia. This case report highlights the necessity of biopsy and histopathological examination for every suspicious cutaneous lesion.

Onychomatricoma masquerading as candidal onychomycosis and paronychia.

Onychomatricoma is a benign slow-growing fibroepithelial tumor arising from the nail matrix. The tumor was described as a new entity almost two decades ago. Although the clinical appearance is typical, most cases are probably misdiagnosed by physicians because of unfamiliarity with the condition. Herein we describe a case of onychomatricoma masquerading as candidal onychomycosis and paronychia and treated erroneously as such.