Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature.

PEComas represent a family of uncommon mesenchymal tumors composed of "perivascular epithelioid cells" with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell "sugar" tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB-45 and/or Melan-A/MART-1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow-up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series.

Autopsy-proven, sporadic pick disease with onset at age 25 years.

CONTEXT: Pick disease is uncommon and accounts for less than 2% of adult-onset dementias. Reports of Pick disease in young adults have apparently increased in the last decade. OBJECTIVE: To document the presentation and course of a patient with tau-positive Pick disease presenting at an extremely young age. SETTING: A university hospital. PATIENT: A white woman with cognitive impairment that began at age 25 years. She experienced progressive dementia over an 8-year period with radiographic evidence of severe cerebral atrophy of the frontotemporal lobes. Autopsy findings confirmed the diagnosis of Pick disease characterized by tau-positive Pick bodies in the neurons of the fascia dentata. CONCLUSION: Pick disease should be considered in the differential diagnosis of young adults presenting with behavioral symptoms, especially those of frontal impairment.

Human DNA topoisomerase I: An anticancer drug target present in human sarcomas.

New anticancer drugs targeting DNA topoisomerase I (topo I) are showing activity against human sarcomas. Laboratory studies have indicated that cells responsive to topo I-targeted drugs have elevated levels of topo I, require active DNA replication, and may require a functional apoptotic pathway. In this study, we evaluated these potential markers of topo I-targeted drug sensitivity in 55 cases of human sarcoma (42 high grade, 4 intermediate grade, and 9 low grade). By immunohistochemical staining, we observed elevated topo I expression in 20 of 55 neoplasms (36%). Immunohistochemical staining for the proliferation marker DNA topoisomerase II-alpha (topo II-alpha), showed that 15 of 55 neoplasms (27%) had topo II-alpha indices >50, indicating a large number of actively cycling tumor cells. Abnormal p53 expression was observed in 19 of the 55 cases (35%). None of the cases were interpreted as positive for ALK-1. To complement our immunohistochemical staining of topo I, we isolated functionally active topo I from extracts of a human sarcoma. These isolates demonstrated that sarcoma topo I is sensitive to topo I-targeted anticancer drugs. Of the 55 cases of human sarcoma, 7 (13%) had high levels of topo I, a large number of cycling tumor cells, and normal p53 expression. These are the molecular parameters that might suggest responsiveness to drugs targeting topo I.