Expression profile of sonic hedgehog signaling-related molecules in basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common human cancer, characterized by aberrant activation of the hedgehog (HH) signaling pathway resulting from mutations in the patched 1 (PTCH1) or smoothened (SMO) genes. In the present study, to uncover the expression profile of HH signaling-related molecules, we thoroughly examined the mRNA and protein expression levels of six molecules including GLI1, GLI2, PTCH1, PTCH2, SHH, and SMO in BCC and various other cutaneous tumors. Real-time PCR analysis demonstrated that BCC showed remarkably enhanced mRNA expression of all HH molecules, except SMO compared to other skin tumors. However, immunohistochemical analysis revealed that only GLI1 protein was specifically upregulated in BCC, while the other HH-related proteins did not show any significant differences between the tumors. Notably, other skin malignancies such as squamous cell carcinoma, sebaceous carcinoma, and malignant melanoma showed no GLI1 expression and there was no difference in GLI1 expression between the BCC subtypes. In addition, GLI1 and GLI2 expression were strongly associated with the hair follicle stem cell markers, LGR4 and LGR5, which are known target genes of the Wnt pathway. Our results suggest that GLI1 has the potential to be a diagnostically useful marker for differentiating BCC from other skin malignancies and an interaction between the HH and Wnt signaling pathways may be involved in the development of BCCs.

GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas.

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.

Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.

Mammalian epidermis, which is composed of hair follicles, sebaceous glands, and interfollicular epidermis, is maintained by discrete stem cells. In vivo lineage tracing demonstrated that murine LGR5 cells are mainly responsible for hair follicle regeneration whereas LGR6 cells generate sebaceous glands and interfollicular epidermis. However, little is known about their expression in the human skin tumors. In this study, we investigated the expression profile of LGR5 and LGR6 in a variety of human skin tumors including basaloid tumors with follicular differentiation (94 basal cell carcinomas, 18 trichoepitheliomas, 3 basaloid follicular hamartomas, and 12 pilomatricomas) and tumors with ductal differentiation (7 eccrine poromas, 8 hidradenomas, and 5 spiradenomas). LGR5 expression was highest in basal cell carcinomas (BCCs) followed by trichoepitheliomas (TEs) and basaloid follicular hamartomas. LGR6 had the same expression pattern as LGR5, even though its expression was lower. Interestingly, LGR6 expression was detected in stromal cells around the tumor and papillary mesenchymal bodies of TEs but not in stromal cells of BCCs, suggesting different characteristics of tumor-associated fibroblasts between TEs and BCCs. It was unexpected to find that pilomatricomas exclusively expressed LGR6, and its expression was limited to the basaloid cells. Notably, LGR6-positive cells were observed in sweat gland ductal cells in normal skin. This might explain, in part, the finding that LGR6 expression was relatively higher in basaloid tumors with ductal differentiation than in those with follicular differentiation. In particular, spiradenomas displayed the same distribution pattern of LGR6 as normal sweat glands, suggesting the possibility of LGR6-positive cells as tumor stem cells. In conclusion, we documented the different expression patterns of stem cell markers, LGR5 and LGR6 in various skin tumors. These data may provide important insights to understand the origin and development of basaloid skin tumors.

Thoracic Presentations of Small Round Blue Cell Tumors.

The term "small round blue cell" is frequently used as a cursory radiologic pathological correlation of aggressive tumors throughout the body. We present a pictorial essay of common and uncommon subtypes of small round blue cell tumors in the chest illustrating the characteristic radiologic findings of each lesion. In addition, we review the pathologic findings of each tumor subtype with characteristic hematoxylin- and eosin-stained photomicrographs and immunohistochemical and molecular studies. Represented tumors include small cell carcinoma, Ewing sarcoma, extranodal marginal zone B-cell lymphoma, embryonal rhabdomyosarcoma, desmoplastic small round cell tumor, and posttransplant lymphoproliferative disorder. Understanding and ability to recognize these lesions are essential to broaden the radiologist's differential diagnosis and help guide patient care.

Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions.

Pulmonary opacities/nodules are common findings on computed tomography examinations, which may represent an underlying infections or malignancy. However, not every pulmonary nodule or opacity represents malignancy or infection. We present a pictorial essay illustrating common as well as obscure noninfectious, nonmalignant pulmonary lesions. Lesions discussed include organizing pneumonia, Langerhans cell histiocytosis, pulmonary amyloidosis, hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibroblastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of these rare lesions.

Evaluating physical and perceptual responses to exergames in Chinese children.

PURPOSE: The primary objective of this study was to examine whether exergames could help children reach the recommendations for PA and cardiorespiratory fitness regarding exercise intensity. Differences in perceived physical exertion, EE, VO2, and HR between normal weight (NW) and overweight (OW) children participating in exergames were also examined. METHODS: Twenty-one children (age: 10.45 ± 0.88) were assessed for EE, VO2 and HR during rest, in a maximal treadmill test, and while playing different exergames. Ratings of perceived exertion (RPE) (category range: 0 to 10) were also measured during exergaming. Three types of exergames were examined: running, table tennis, and dancing. These games were either performed on a Chinese game console, I-Dong, or another well-developed Western game console (Sony PlayStation 3 or Nintendo Wii). RESULTS: Exergaming resulted in EE (kcal/min) from 2.05-5.14, VO2 (mL/kg/min) from 9.98-25.54, and HR (beats per minute) from 98.05-149.66. Children reported RPE ranging from 1.29 to 5.29. The Chinese exergame, I-Dong Running, was the only game in which children reached a moderate intensity and met the recommended minimum VO2reserve (50%) for cardiorespiratory fitness. CONCLUSION: Exergames could provide alternative opportunities to enhance children's physical activity. They could be used as light-to-moderate PA, and with exergames, children can even reach the recommended intensity for developing and maintaining cardiorespiratory fitness.

Incidental hyperdensities within the reticuloendothelial system.

This is a case report of a 79-year-old woman who was found to have numerous hyperdense nodular lesions in the upper abdomen, which were incidentally discovered during routine follow-up of a lung nodule. These hyperdense lesions included a lace-like reticular distribution within the liver, multiple extremely dense lymph nodes, and a shrunken hyperdense spleen. We discuss differential considerations for such a constellation of findings and explain why we believe the findings in this case are consistent with prior thorium dioxide exposure. We conclude with a discussion of the pathophysiology and important complications of thorium dioxide exposure and the best imaging modalities for its detection. We believe that this is an important entity that all physicians should be aware of because even though it is seldom seen today, it has characteristic imaging findings and the correct diagnosis is critical given the increased risk of malignancy for which such patients should be screened for.

Recurrent bronchioloalveolar carcinoma after lung transplantation: radiographic and histologic features of the primary and recurrent tumors.

The chest radiographs of the original and recurrent BAC after lung transplantation in 3 patients were reviewed for correlation with their histologic patterns. The radiographs of non-mucinous BACs in 2 patients were manifested as nodules of variable size, whereas that of mucinous BAC in 1 patient was characterized as hazy opacities. One of the non-mucinous BACs was papillary while the other was lepidic. The original and recurrent tumors were identical radiographically and histologically in the same patients. The study supports the notion that the recurrent BACs found in the donor lungs originated in the recipient.