FISH for MYC amplification and anti-MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations.

BACKGROUND: Secondary angiosarcoma and benign but microscopically atypical vascular proliferations (herein referred to as atypical vascular lesion or AVL) are rare consequences of radiation therapy and/or chronic lymphedema most commonly seen in breast cancer patients. Differentiating angiosarcoma from AVL can be difficult due to overlapping clinical and microscopic features. Recently, amplification of MYC has been associated with 55-100% of secondary angiosarcomas but is reportedly absent in AVL. We examined a series of secondary angiosarcoma and AVL for MYC amplification by fluorescence in situ hybridization (FISH) and expression by immunohistochemistry to investigate the diagnostic utility for discriminating angiosarcoma from AVL. METHODS: Cases of secondary angiosarcoma (n = 8) and AVL (n = 4) were retrieved from our archives and examined by FISH and immunohistochemistry. RESULTS: All angiosarcoma cases (8/8 = 100%) demonstrated high-level MYC amplification by FISH, whereas all AVLs (0/4 = 0%) were negative for MYC amplification. Additionally, all angiosarcoma cases (8/8 = 100%) demonstrated nuclear positivity for MYC, whereas all AVLs (0/4 = 0%) were negative. CONCLUSION: Amplification of MYC and nuclear expression of MYC is present in secondary angiosarcoma but not AVL. These ancillary tests can be useful to distinguish angiosarcoma from AVL in difficult cases.

Esophageal submucosa: the watershed for esophageal cancer.

OBJECTIVES: Submucosal esophageal cancers (pT1b) are considered superficial, implying good survival. However, some are advanced, metastasizing to regional lymph nodes. Interplay of cancer characteristics and lymphatic anatomy may create a watershed, demarcating low-risk from high-risk cancers. Therefore, we characterized submucosal cancers according to depth of invasion and identified those with high likelihood of lymph node metastases and poor survival. METHODS: From 1983 to 2010, 120 patients underwent esophagectomy for submucosal cancers at Cleveland Clinic. Correlations were sought among cancer characteristics (location, dimensions, histopathologic cell type, histologic grade, and lymphovascular invasion [LVI]), and their associations with lymph node metastasis were identified by logistic regression. Associations with mortality were identified by Cox regression. RESULTS: As submucosal invasion increased, cancer length (P < .001), width (P < .001), area (P < .001), LVI (P = .007), and grade (P = .05) increased. Invasion of the deep submucosa (P < .001) and LVI (P = .06) predicted lymph node metastases: 45% (23/51) of deep versus 10% (3/29) of middle-third and 7.5% (3/40) of inner-third cancers had lymph node metastases, as did 46% (12/26) with LVI versus 18% (17/94) without. Older age and lymph node metastases predicted worse 5-year survival: 94% for younger pN0 patients, 62% for older pN0 patients, and 36% for pN1-2 patients regardless of age. CONCLUSIONS: Submucosal cancer characteristics and lymphatic anatomy create a watershed for regional lymph node metastases in the deep submucosa. This previously unrecognized divide distinguishes superficial submucosal cancers with good survival from deep submucosal cancers with poor survival. Aggressive therapy of more superficial cancers is critical before submucosal invasion occurs.