Adolescent Onset of Localized Papillomatosis, Lymphedema, and Multiple Beta-Papillomavirus Infection: Epidermal Nevus, Segmental Lymphedema Praecox, or Verrucosis? A Case Report and Case Series of Epidermal Nevi.

Herein, we report the case of a 12-year-old female who noted the recent onset of an oval, circumscribed, 10-cm papillomatous plaque affecting the thigh and vulva that showed histologic signs of lymphedema without evidence of secondary lymphedema. The sequencing of genes associated with a delayed onset of lymphedema or epidermal nevi (EN) - GATA2 and GJC2, and HRAS and KRAS, respectively - showed wild-type alleles. Polymerase chain reaction for human papillomavirus (HPV) DNA demonstrated infections with 15 HPV genotypes. Evidence of productive HPV infection, HPV capsid expression, and cytopathic changes was detected. At the 6-month follow-up, no evidence of recurrence was found after complete excision. The analysis of a consecutive series of 91 EN excision specimens revealed that 76% exhibited histologic evidence of lymphostasis. Notably, multiple acrochordon-like EN, which most closely resembled this case, showed similar signs of localized lymphedema. The late onset and evidence of lymphedema favors the diagnosis of congenital unisegmental lymphedema. However, the clinical findings and epidermal changes point to the diagnosis of EN. Moreover, localized verrucosis also accurately describes this patient's cutaneous findings. Based on the above evidence, we postulate that an abnormal development of lymphatics may play a primary role in the pathogenesis of some types of EN and facilitate productive HPV infection.

Molecular diagnostics in melanoma.

Molecular pathology is rapidly evolving, featuring continuous technologic improvements that offer novel clinical opportunities for the recognition of disease predisposition, for identifying sub-clinical disease, for more accurate diagnosis, for selecting efficacious and non-toxic therapy, and for monitoring of disease outcome. Currently, the identification and prognosis of primary cutaneous melanoma is based on histologic factors (tumor depth and ulceration) and clinical factors (number of lymph node and/or distant metastases). However, metastasis can occur in patients with thin melanomas, and sentinel lymph node biopsy does not identify all patients at risk for distant metastasis. New markers exist that correlate with melanoma progression, which may aid in melanoma identification, prognostication, and detection of minimal residual disease/early recurrence. Moreover, not many therapeutic options exist for melanoma as no regimen prolongs survival. Emerging data with investigational therapies suggest that certain markers might play a crucial role in identifying patients who will respond to therapy or show utility in the monitoring the response to therapy. Herein, molecular diagnostics that can potentially benefit the individual melanoma patient will be discussed.

Malignant melanoma 2003: predisposition, diagnosis, prognosis, and staging.

The incidence and mortality of melanoma has seemed to level off for certain groups after a steady increase during the last 50 years. This trend is suspected to be secondary to education efforts aimed at prevention and better detection and removal of thin, biologically benign melanomas. Since no effective systemic therapies exist for metastatic melanoma, early detection and removal of thin melanomas offer the best chance of cure. For thicker melanomas, sentinel lymph node biopsy has improved the accuracy of staging and prognostic evaluation. However, approximately one third of patients diagnosed with metastatic melanomas present without previous regional lymph node metastases. As the genomic understanding of melanoma's pathogenesis grows, new methods likely will be developed to more accurately identify the people at risk for melanoma, those who have high-risk melanomas, and those who have disseminated disease. We review current and potential biomarkers useful for the screening for and prevention, diagnosis, staging, and prognosis of melanoma.