Genomic comparison of malignant melanoma and atypical Spitz tumor in the pediatric population.

BACKGROUND/OBJECTIVES: The diagnostic distinction between atypical Spitz tumor (AST) and malignant melanoma (MM) in pediatric tumors is challenging. Molecular tests are increasingly used to characterize these neoplasms; however, limited studies are available in pediatric patients. This study aimed to provide a genomic comparison of pediatric MM and AST in the context of comprehensive clinical annotation. METHODS: Pediatric patients diagnosed with MM (n=11) and AST (n=12) were compared to a cohort of 693 adult melanoma patients. DNA next-generation sequencing assessed kinase gene fusions, tumor mutational burden, sequence variants, copy number alterations, structural variants, microsatellite instability, and mutational signatures. RESULTS: Seven AST cases and eight MM cases were successfully sequenced. Kinase gene fusions were identified in both the MM and AST cohorts (NTRK1, ROS1, and MET). MM cases had TERT, BRAF, and CDKN2A alterations, which were not identified in the AST cohort. Tumor mutational burden (TMB) analysis showed pediatric ASTs had an average of 2.82 mutations/Mb, pediatric MM had an average of 5.7 mutations/Mb, and adult MM cases averaged 18.8 mut/Mb. One pediatric MM case had an elevated TMB of 15 mutations/Mb and a UV mutational signature. CONCLUSIONS: These data expand our understanding of pediatric malignant melanoma. The differences between the molecular signatures for AST and MM are not statistically significant, and histopathology remains the gold standard for the diagnosis of pediatric AST and MM at this time. With more data, molecular studies may provide additional support for diagnosis and targeted therapeutics.

Verrucous Venous Malformation-Subcutaneous Variant.

BACKGROUND: Verrucous venous malformation (VVM), previously called "verrucous hemangioma," typically involves the dermis and the subcutaneous fat. We have encountered patients with VVM confined to the hypodermis. MATERIALS AND METHODS: During a nearly 20-year period, 13 patients, aged 2-17 years, presented with a subcutaneous mass in the limb without clinically obvious epidermal alterations. Consequently, operative excisions did not include the skin. RESULTS: Histopathologically, the specimens were composed of blood-filled channels with morphologic characteristics of capillaries and veins that infiltrated adipose tissue. Aggregates often formed nodules with variable fibrosis and a component of large and radially oriented vessels. A diagnosis of VVM was supported by endothelial immunopositivity for GLUT-1 (25%-75% immunopositive channels in 16/16 specimens); D2-40 (1%-25% channels in 14/15 specimens); and Prox-1 (1%-50% of channels in 14/16 specimens). A MAP3K3 mutation was identified by droplet digital PCR in 3 of the 6 specimens. CONCLUSIONS: Diagnosis of VVM in this uncommon location is challenging because of absence of epidermal changes and lack of dermal involvement. Imaging is not pathognomonic, and mimickers are many. Appropriate immunohistochemical stains and molecular analysis contribute to the correct diagnosis.

Pemphigus-like eruption as a complication of molluscum contagiosum treatment with imiquimod in a 5-year-old girl.

Pemphigus and pemphigus-like reactions can be triggered by a variety of medications including topical therapies, such as imiquimod. While the association between imiquimod and pemphigus-like reactions has been reported in adults, this is the first report of a generalized reaction beyond the site of imiquimod application in a child. The mechanism by which this occurs may be through a unique pathway, separate from the classic antibody-mediated pathway. Our patient had a full recovery without recurrence after cessation of the inciting drug.

Eosinophilic annular erythema treated with dupilumab.

Eosinophilic annular erythema is a rare, benign, recurrent condition characterized by annular skin lesions, tissue eosinophilia, and resistance to a variety of treatments. There are fewer than 30 cases reported in the English literature, 7 of which are in children. We present a case of recurrent eosinophilic annular erythema in an adolescent that was successfully treated with dupilumab, an interleukin-4 receptor alpha antagonist.

A case of neonatal sweet syndrome associated with mevalonate kinase deficiency.

BACKGROUND: Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS. CASE PRESENTATION: Through a multidisciplinary approach, this patient was also found to have very early onset inflammatory bowel disease (VEO-IBD) and Mevalonate kinase-associated disease (MKAD). While prior case studies have characterized an association between VEO-IBD and MKAD, there is no literature describing the association of all three diagnoses this case: H-SS, VEO-IBD and MKAD. Initiation of canakinumab in this patient resulted in successful control of the disease. CONCLUSIONS: This case highlights the importance of a multidisciplinary approach to rare diagnoses, and collaboration during cases with significant diagnostic uncertainty.

Pediatric Lichen Myxedematosus: A Diagnostic and Management Challenge.

Localized lichen myxedematosus (LM) is a rare, idiopathic mucinosis characterized by dermal mucin deposition and variable fibroblast proliferation. Nodular lichen myxedematosus, a clinicopathologic subtype of localized LM, is exceedingly rare in pediatric patients with only three prior cases reported. Understanding of LM in pediatric patients is limited by the rarity of the disease, and diagnosis is complicated by overlapping clinical and histopathologic features. There is no standardized treatment for localized LM and treatment is largely dictated by a patient's desire to minimize cosmetic disfigurement. This case series reports two additional patients with juvenile nodular lichen myxedematosus, highlights the limitations of existing diagnostic criteria, and describes successful treatment of one patient with intralesional triamcinolone.

Management of Residual Spitz Nevus in Surgical Specimens following Biopsy and Excision.

Proper management of Spitz nevi continues to be debated, with treatment ranging from observation to surgery. To better characterize the outcome of surgical procedures performed for incomplete initial excision or biopsy, we sought to ascertain the histopathological presence of residual Spitz nevi in a set of surgical specimens. METHODS: We retrospectively reviewed 123 records with histologically-confirmed Spitz nevus. Data concerning treatment, clinical features, histopathological margin involvement, and presence of residual lesion on subsequent procedural specimens were collected. RESULTS: Fifty-three percent of lesions (n = 65) were initially sampled by shave or punch biopsy, and the remainder (n = 58) were formally excised without initial biopsy. The rates of re-excision for involved margins were: shave biopsy (92.2%), punch biopsy (78.6%), and formal excision (13.8%). In total, 61.0% of patients who underwent an initial procedure of any kind had involved margins, but only half of those re-excised for involved margins (57.6%) had histologically residual lesion on repeated excision. A significantly higher proportion of initial punch biopsies (90.9%) resulted in residual lesion (in secondary excision specimens) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < 0.05). CONCLUSIONS: Findings suggest that clinicians may consider shave biopsy over punch biopsy for diagnosing suspected lesions, when indicated and appropriate. Given the rarity of malignant transformation and the frequency of residual nevus, observation may be reasonable for managing pediatric patients with histologically-confirmed Spitz nevi, who are post initial biopsy or excision despite known histopathological margin involvement.

Infantile digital fibromatosis.

Infantile digital fibromas are rare benign neoplasms that occur principally in children and are usually confined to the digits. These lesions are similar in appearance to several benign and malignant lesions, and biopsy is often required to confirm the diagnosis. The tumor is composed of myofibroblasts, which contain pathognomonic intracellular inclusion bodies. There is a strong tendency for recurrence after excision. We present a 2-year-old who developed extensive involvement of all 4 extremities after syndactyly release. This case is unusual in that the lesions occurred postsurgically and were substantially more extensive than those previously described.

Nodular Foot Myxedema Masquerading as Lymphedema.

Lymphedema results from abnormal development or injury to the lymphatic system. One-fourth of patients with lower extremity enlargement are erroneously labeled with "lymphedema." We describe a patient with hypothyroidism who developed soft-tissue overgrowth of her foot. She was referred to our Lymphedema Program for management of "lymphedema" and overgrown toes. The patient's lymphoscintigram showed normal lymphatic function in her extremities, and she was diagnosed with myxedema by histopathology. Nodular localized myxedema should be included in the differential diagnosis of lymphedema.