Faculty Bibliography

Primary cutaneous carcinosarcoma is a rare biphenotypic neoplasm exhibiting both epithelial and sarcomatous elements. Even though its origin and biological aspects remain poorly understood, it has been postulated that this tumor may arise from progenitor cells, which subsequently differentiate into distinct tumor components. We have investigated the histological and immunohistochemical staining patterns of a cutaneous carcinosarcoma case, as well as its ultrastructural aspects. In addition, sarcomatous and epithelial tumor components were separated by laser capture microdissection and subjected to targeted, high-depth, next-generation sequencing of a 46-cancer gene panel to asses the gene mutational pattern amongst both components. There were transitional cells at the epithelial/mesenchymal transition that labeled with putative progenitor cell markers (K19, c-kit, CD34 and Bcl-2). There was shared reactivity to antibodies directed against the progenitor cell marker EpCAM (epithelial cell adhesion molecule) in both components. Ultrastructurally, individual cells were demonstrated to have overlapping features of epithelial and mesenchymal differentiation. The mutational analysis revealed point mutations in exon 5 of TP53, which were identical in both the epithelial and sarcomatous components, and which were concordant with p53 expression at a tissue level. The aforementioned histological, ultrastructural, immunohistochemical and mutational pattern is strongly suggestive of a common clonal origin to the distinct elements of this tumor.

BACKGROUND:The hallmark of lung ischemia-reperfusion injury (IRI) is the production of reactive oxygen species (ROS), and the resultant oxidant stress has been implicated in apoptotic cell death as well as subsequent development of inflammation. Dietary flaxseed (FS) is a rich source of naturally occurring antioxidants and has been shown to reduce lung IRI in mice. However, the mechanisms underlying the protective effects of FS in IRI remain to be determined. METHODS:We used a mouse model of IRI with 60 min of ischemia followed by 180 min of reperfusion and evaluated the anti-apoptotic and anti-inflammatory effects of 10% FS dietary supplementation. RESULTS:Mice fed 10% FS undergoing lung IRI had significantly lower levels of caspases and decreased apoptotic activity compared with mice fed 0% FS. Lung homogenates and bronchoalveolar lavage fluid analysis demonstrated significantly reduced inflammatory infiltrate in mice fed with 10% FS diet. Additionally, 10% FS treated mice showed significantly increased expression of antioxidant enzymes and decreased markers of lung injury. CONCLUSIONS:We conclude that dietary FS is protective against lung IRI in a clinically relevant murine model, and this protective effect may in part be mediated by the inhibition of apoptosis and inflammation.

Von Zumbusch generalized pustular psoriasis (GPP) is the most severe type of psoriasis with possible life-threatening complications. We report the case of a 22-year-old woman who presented with a severe eruption of generalized pustular psoriasis 48 hours after receiving an injection of etanercept (Enbrel).

OBJECTIVES/OBJECTIVE:Neuroendocrine tumors (NETs) are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC) are exceedingly rare. MATERIALS AND METHODS/METHODS:The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. RESULTS:Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma) can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. CONCLUSIONS:A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

OBJECTIVES/OBJECTIVE:To report cases of primary neuroendocrine tumours (NETs) of the kidney, including carcinoid tumour, large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCC), which show a wide range of NE differentiation and biological behaviour, and are exceedingly rare. PATIENTS AND METHODS/METHODS:The clinicopathological features of all nine renal NETs diagnosed during a 7-year period were reviewed. RESULTS:Six carcinoids, two SCC and one LCNEC were identified from 2780 kidney tumours. No patient had carcinoid syndrome or other NE symptoms. Three of six carcinoids and no SCC/LCNEC arose in horseshoe kidneys. The mean size of the six carcinoids and three SCC/LCNEC was 4.8 cm and 12.2 cm, respectively. No carcinoid had tumour necrosis or mitosis. By contrast, three SCC/LCNEC had extensive tumour necrosis and brisk mitosis. All renal NETs were positive for synaptophysin but were variably positive for chromogranin and CD56. Three of six carcinoid tumours were confined to the kidney, and four of five patients were disease-free at a mean (range) of 26 (6-74) months. One patient with nodal metastases has had no recurrence and another died with liver metastases. Three patients with SCC/LCNEC each presented with locally advanced disease and extensive lymphadenopathy; two of them died from distant metastasis or local tumour progression, and the third is currently alive with disease. CONCLUSIONS:Various NETs can occur in the kidney, but rarely. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. The diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical NE markers.