PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma.

Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of nevus spilus and capillary malformation syndromes, paving the way for better clinical management.

Post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified in a pediatric patient.

Solid organ and hematopoietic stem cell transplantation may be complicated by the development of post-transplant lymphoproliferative disorders (PTLDs). The World Health Organization categorizes PTLDs into four entities including non-destructive, monomorphic, polymorphic, and classical Hodgkin lymphoma types. The most common PTLDs are B-cell lymphomas, with T-cell lymphomas accounting for only a few cases. Cutaneous T-cell lymphomas are rarer still in post-transplant patients with primary cutaneous peripheral T-cell lymphoma being an extraordinarily rare subtype in this population. PTLDs may be aggressive and are often associated with high morbidity and mortality. Advances in medicine have led to increased awareness of PTLDs and improved diagnostic tools which assist in the diagnosis of these conditions. However, the clinical and histopathologic heterogeneity of PTLDs may make diagnosis a challenge. In the transplant patient population, the cutaneous manifestations of the lymphoproliferative disease may mimic other conditions, such as eczematous dermatitis and graft-vs-host disease. Herein, we report a case of post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in a pediatric heart transplant patient and describe the clinical presentation and diagnostic histopathologic features.

A sixteen-year single-center retrospective chart review of Spitz nevi and spitzoid neoplasms in pediatric patients.

BACKGROUND: Spitzoid neoplasms in pediatric patients pose an interesting challenge for clinicians. More data on the clinical, histologic, and molecular characteristics of these lesions are necessary to distinguish features that may portend recurrence or malignant behavior to help determine future treatment guidelines in pediatric patients. METHODS: Institutional Review Board approval was obtained from Children's Hospital of Wisconsin to conduct a retrospective analysis of spitzoid neoplasms. Patients with biopsied or excised spitzoid neoplasms between 01/01/2000 and 08/01/2016 were included. Pertinent clinical and histologic data were collected. Atypical, unusual, or diagnostically uncertain lesions were selected for re-review. RESULTS: 266 lesions from 264 patients were included. 243 were classified as benign (91.35%), 22 as atypical (8.27%), and 1 as spitzoid melanoma (0.38%). No clinical or histologic variables were found to be statistically significant between the benign Spitz, atypical Spitz, and spitzoid melanoma cohorts. No known deaths occurred. CONCLUSION: Our findings highlight the extreme variability of spitzoid neoplasms clinically and histologically. Importantly, this study demonstrates that the vast majority of spitzoid neoplasms in pediatric populations are benign and supports conservative management of spitzoid lesions in children.

Cutaneous spindled follicle center cell lymphoma with abundant mucin: A diagnostic pitfall.

Primary cutaneous follicle center cell lymphoma is the most prevalent type of primary cutaneous B-cell lymphoma and usually portends a favorable prognosis. Typically, the diagnosis can be rendered based on characteristic histopathologic features and immunohistochemical profile. Rarely, a diagnostically challenging variant with a predominant spindle morphology mimicking other malignant spindle cell neoplasms may be encountered. Even more unusual is the presence of a prominent myxoid stroma in this rare sarcomatoid variant of follicle center cell lymphoma. Herein, we present a case of a 52-year-old man with a slowly enlarging cyst-like lesion on the chin with histopathologic examination revealing a malignant, predominantly spindled neoplasm within an abundant myxoid stroma. Following a broad panel of immunohistochemical stains, the strong positive staining of the spindle cells for LCA (CD45), CD20, and Bcl-6 confirmed the diagnosis of follicle center cell lymphoma. We present this distinctive rare subtype of cutaneous follicle center cell lymphoma to increase awareness of this variant and to discuss challenging histopathologic mimics to consider while highlighting the utility of immunohistochemistry stains to avoid misdiagnosis.

Acute, Temporary, Unilateral Facial Nerve Palsy After Dermatologic Surgery: A Report of 3 Cases.

Facial nerve dysfunction can be functionally and cosmetically debilitating and is commonly associated with high anxiety for patients. We report 3 cases of temporary, unilateral facial nerve palsy following dermatologic surgery under local anaesthesia over the preauricular cheek and mandibular angle, which, to our knowledge, has not been reported in the literature. Given its frightening presentation mimicking a stroke, it is essential for dermatologists to become aware of this complication to inform their patients more thoroughly. Thus, when performing facial surgery over these regions, we recommend that dermatologists include this rare complication and its good prognosis in the consenting process to minimise anxiety for those who experience it intra- or postoperatively.