Influence of surgical trauma on experimental metastasis in healing wounds is investigated using a transplantable murine mammary carcinoma cell line, TA3Ha. Intravenous injection of 10(5), 10(6), and 2 x 10(6) TA3Ha cells into syngeneic Strain A mice led to liver or kidney tumor development in none of the 96, ten, and ten mice tested, respectively. In contrast, injection of 10(5) cells into mice immediately after hepatic wedge resection performed using milliwatt carbon dioxide laser and electrocautery resulted in tumor formation at the site of trauma in 21/37 (57%) and 25/52 (48%) mice, (P less than 0.001) respectively. Similar results were obtained in mice subjected to partial nephrectomy using the laser (nine of 18) and electrocautery (eight of 13). These results clearly demonstrate that surgical trauma renders a nonprivileged organ susceptible to experimental metastasis formation, and that at least in this model both laser and electrocautery have similar effects. Tumor cell injection 1, 7, and 10 days posthepatic surgery resulted in 36%, 20%, and 0% tumor formation, respectively, indicating that the earlier events in wound healing support tumor implantation and/or growth better than those later on. Frequency of tumor formation at sites of trauma in the peritoneum induced by scalpel blade, laser, and electrocautery were 28%, 50% and 82%, respectively. Peritoneal tumors were seen in 33% of the nonsurgical mice. Skin incisions induced with the three above probes had little influence on experimental metastasis formation. Thus the influence of trauma on tumor formation is not uniform in every organ.

The presence of occult metastases shortened the disease-free interval and suggested that more diligent axillary staging would more accurately identify patients who would benefit from systemic adjuvant treatment.

No abstract

This report describes four malignant tumors originating in infants, (one present at birth), for which a common origin is proposed. The common nature of these tumors was suggested by a remarkable similarity of histologic and ultrastructural features, including the presence of intracellular filamentous aggregates, as well as a shared aggressive clinical course consistent with sarcomatous origin. Two of these neoplasms arose within the kidney and were classified as “rhabdoid” sarcomas, according to the NWTS nomenclature. However, cells from these neoplasms could not be identified as muscular in origin. In culture, these cells demonstrated adherence to substratum, ability to phagocytose particles, and cell surface complement receptors. In addition, the renal tumors contained definite tumor cells positive for muramidase; the liver primary tumor contained only a limited number of such cells, which could not be interpreted as neoplastic. These findings suggest that among the “round‐cell sarcomas” of infants and young children, a distinct, highly malignant form may be identified on clinical and morphologic grounds. The possibility that the tumor cells may be linked to the mononuclear phagocyte system was suggested, but not proved, and deserves further study.

The widespread utilization of screening mammography has produced a shift in the stage of breast cancer at diagnosis in the US: Currently, 12% to 15% of newly diagnosed breast cancer cases annually are ductal carcinoma in-situ (DCIS). The diagnosis is made, in at least 90% of patients, with mammography. Only about 10% of patients will have a palpable mass. The accurate characterization and visualization of calcifications typically requires magnification of mammographic imaging. The morphology of the calcifications is generally considered to be the most important factor in differentiating benign from malignant formations. Round and uniform shapes are more likely to be benign, while linear and heterogeneous morphologies are associated with DCIS. Following a complete mammographic work-up, most suspicious lesions are potential candidates for a stereotactic core needle biopsy. Ten percent to 50% of patients initially diagnosed with atypical ductal hyperplasia by needle biopsy have subsequently been surgically diagnosed with cancer near the biopsy site. Due to this relatively high incidence of co-existent carcinoma, a needle biopsy diagnosis of atypical ductal hyperplasia necessitates subsequent surgical excision. The most important change in our thinking about DCIS was from a monolithic view, conceiving of DCIS as a single disease highly likely to invade if left untreated, to the realization that DCIS represents a non-obligate precursor with a variable risk of progression, depending on a combination of factors, such as histology, lesion, size, and margin status. In discussing treatment options, patients should understand that local recurrence following total mastectomy is rare and that this is the procedure of choice for disease that cannot be adequately encompassed with a breast-conserving approach. If the patient and her surgeon are in agreement about proceeding with a breast-conserving approach, there needs to be a clear understanding of the incidence and implications of local recurrence. In all such discussions with newly diagnosed patients, however, it is essential to emphasize the excellent prognosis with this disease, irrespective of the surgical approach.

Alveolar rhabdomyosarcoma (ARMS) is remarkably rare in adults over 45 years. Initial immunoprofiling of a small cell neoplasm of the head and neck region in an older adult may not include myogenic markers. A valuable diagnostic aid and important prognostic parameter in ARMS is the identification of PAX3-FOXO1 [t(2;13)(q35;q14)] or PAX7-FOXO1 [t(1;13)(p36;q14)] rearrangements. The purpose of this study was to document the clinicopathologic, immunophenotypic, and genetic features of head/neck ARMS in older adults. Prior isolated descriptions of three patients were included. Five patients were female and two male (median age 61 years). Each neoplasm was composed of undifferentiated, small round cells in a predominantly solid pattern. Initially ordered immunostains corresponded with early diagnostic impressions of a hematologic malignancy or neuroendocrine carcinoma. CD56 was positive in 5/5 tumors and synaptophysin in 1/6. Given the virtual absence of other lymphoid or epithelial markers, muscle immunostains were performed and these were positive. Definitive ARMS diagnoses were confirmed genetically. This study illustrates the diagnosis of head/neck ARMS in older adults is complicated by its rarity, lack of an alveolar pattern, and a potentially misleading immunoprofile (CD56 and synaptophysin immunoreactivity) if myogenic markers are not employed. Both PAX3-and PAX7-FOXO1 ARMSs were identified in these patients. In children, PAX7-FOXO1 ARMS is associated with a significantly longer event-free survival. In contrast, adult ARMS behaves more aggressively with a worse overall survival than pediatric ARMS. Further follow-up and additional cases are required to assess the prognostic relevance of these fusion transcripts in the context of advanced age.

Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy. The aim of this study was to evaluate the prognostic value of molecular subtyping using MammaPrint and BluePrint in women with early-stage breast cancer (BC) treated at US institutions following National Comprehensive Cancer Network standard guidelines. Tumor samples were collected from stage 1-2B consecutively diagnosed BC patients (n = 373) who underwent lumpectomy or mastectomy with an axillary staging procedure between 1992 and 2010 at two institutes (NorthShore University HealthSystem and Fox Chase Cancer Center) in the United States of America, with a median follow-up time of 9.5 years. MammaPrint low-risk patients had a 10-year DMFS of 96 % (95 %CI 92.8–99.4), while MammaPrint high-risk patients had a 10-year DMFS of 87 % (95 %CI 81.9–92.1) with a hazard ratio of 3.62 (95 %CI 1.38–9.50) (p = 0.005). Uni- and multivariate analyses included age, tumor size, grade, ER, and Her2; in multivariate analysis, MammaPrint reached near-significance (HR 3.01; p 0.08). When comparing BluePrint molecular subtyping with clinical stratification, the prognosis (10-year DMFS) was significantly different in 10-year DMFS between the different molecular subtypes (p < 0.001). This retrospective study with 10-year follow-up data provides valuable insight into prognosis of patients with primary BC comparing clinical with molecular subtyping. The BluePrint molecular stratification assay identifies patients with significantly different outcomes compared with standard clinical molecular stratification.

Background. The recurrence or mortality rate of axillary lymph node‐negative invasive breast cancer has been associated with the tumor S‐phase fraction, which is measured by DNA flow cytometry. Because many of the studies that established this association were performed using frozen, pulverized tumor specimens, this association could not be tested for independence from the established prognostic factors of histologic and nuclear grading. Methods. Histologic, nuclear, and mitotic grades, DNA ploidy, and S‐phase fraction (SPF) were determined from paraffin‐embedded tumors obtained from 280 women with node‐negative invasive ductal carcinomas using standard grading schemes and flow cytometric techniques. These variables were compared with disease‐free and cancer‐specific survival (CSS) in univariate and multivariate analyses of these patients. Results. Tumor diameter, SPF, histologic grade, and nuclear grade were significant predictors of disease‐free survival (OFS); diameter and SPF had significant associations with CSS. Cox analysis showed histologic grade to be the only independent predictor of relapse, whereas diameter and SPF were independent predictors of mortality. The patients with low nuclear or histologic grade tumors had only a 5% risk of recurrence at 5 years. In contrast, 36% of patients in this series with medium‐grade or high‐grade high SPF tumors had a 30% risk of recurrence over the same interval. Conclusions. Histopathologic grading and flow cytometric determination of SPF appear to provide additive prognostic information for patients with early invasive ductal carcinomas of the breast.