Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score.

BACKGROUND: Immunohistological assessment of Ki 67 expression is less expensive than Oncotype Dx, which is currently used to identify patients with lymph node-negative breast cancer, who will benefit from adjuvant chemotherapy. METHODS: The relationship of immunohistologically measured Ki 67 to Oncotype DX recurrence score (RS) was examined in 53 cases of T1-2 N0 M0 (oestrogen receptor-positive, HER2/neu negative) breast cancer. RESULTS: There was a strong linear correlation between Ki 67 value and the Oncotype Dx RS. All patients in the low Ki 67 group (Ki 67 of ≤ 10%) had Oncotype Dx RSs of low or intermediate risk. The vast majority of patients (93.8%) in the high-Ki 67 group (Ki 67 ≥ 25%) had oncotype RSs of high or intermediate risk. CONCLUSION: Ki 67 proliferation value is a major, but not the sole determinant of Oncotype Dx score.

Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study.

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.

Metastatic carcinoma resulting in hepar lobatum.

Hepar lobatum is an acquired liver deformity mostly known as the end-stage of tertiary syphilis. The authors report two cases of hepar lobatum resulting from metastatic mammary ductal carcinoma in the liver and reassess the clinicopathologic features of seven previously reported cases (two in the German language). A liver of near-normal weight with an irregularly lobulated contour, capsular indentations/crevices from which intersecting (carcinoma-bearing) fibrous septa extended deep into the parenchyma, a predominant centrifugal distribution of lesional areas, and many septa abutting on the degenerated center of tumor nodules were the salient gross features. No significant tumor/fibrous occlusion of intrahepatic branches of portal or hepatic veins, nor cirrhotic type nodular hepatocellular regeneration was observed. Both of these patients experienced a drastic decrease in CEA serum levels during multiagent palliative chemotherapy. In one patient, abundant macrophages in conjunction with minimal residual tumor were present within intrahepatic septa. The pathogenesis of this condition appears largely related to an active phase of chemo-induced tumor regression with subsequent tissue collapse, followed by an organizing phase of healing and scar contraction.

Spontaneous temporary remission in primary CNS lymphoma.

We report a case of primary CNS lymphoma in which complete, though temporary, spontaneous clinical and radiologic remission occurred. This is the first such case report to our knowledge.

Wegener's granulomatosis presenting as temporal arteritis.

A granulomatous giant cell vasculitis of the temporal artery was observed in a biopsy specimen from a patient with corresponding clinical symptoms. Within weeks, the new onset of pulmonary infiltrates and renal failure prompted biopsy of the patient's kidney. A necrotizing glomerulonephritis, compatible with a diagnosis of Wegener's granulomatosis, was present. Vasculitis of the temporal artery may be a feature of Wegener's granulomatosis.

Primary malignant lymphoma of the central nervous system.

Between 1960 and 1983, 19 patients with primary malignant lymphoma of the central nervous system (CNS) were seen at McGill University Hospitals. The diagnosis was made at autopsy in 3 patients, and by biopsy in 16. Results of treatment were poor. All four patient who underwent surgery alone died within 2 months of diagnosis. Of 12 patients who underwent surgery and postoperative radiotherapy, 11 died between 2 and 56 months (median, 12 months) following diagnosis, and one is alive with disease at 47 months. Patterns of involvement at first recurrence and/or at autopsy were analyzed for 13 patients. Failure at the original site of involvement was unusual after treatment consisting of surgery and radiotherapy. In contrast, failure in the brain at sites other than those originally involved was common in spite of the use of whole brain irradiation. Local leptomeningeal involvement was seen in one patient whose diagnosis was made at autopsy, and cerebral spinal fluid seeding was seen in two additional patients, one within 1 month of diagnosis and one at relapse at 6 months after diagnosis. No patient developed disease outside the CNS. The limitations of current therapy for this disease are discussed, and certain suggestions made regarding the management of future patients with this diagnosis.

Monoclonal anti-CEA antibodies in the discrimination between primary pulmonary adenocarcinoma and colon carcinoma metastatic to the lung.

Lung metastases from colon adenocarcinoma are often difficult to differentiate from primary lung adenocarcinoma. We studied the diagnostic value of a polyclonal anti-CEA antiserum and two monoclonal anti-CEA antibodies (B18, D14) which define antigens overexpressed in colon carcinoma. Autopsy material from 20 patients with colon carcinoma and lung metastases and 20 specimens from patients with primary lung adenocarcinoma were retrieved, stained, and interpreted without knowledge of the origin of the lung tumor. Colon carcinomas, lung metastases and lung primaries stained positively with polyclonal anti-CEA in 90-100% of cases. D14 stained 75% of colonic metastases and 70% of primary lung adenocarcinomas, whereas 95% of colon primaries were positive. Sixty-five percent of colon primaries and 50% of their metastases were positive with B18, whereas 45% of lung primaries were positive. The frequency of B18 positivity was significantly greater in those colon primaries that were surgically derived (7/9, 78%) compared with their autopsy-derived lung metastases (2/9, 22%) (P less than 0.05). Similarly, D14 staining in surgically derived colon primaries (9/9, 100%) was significantly greater than their autopsy-derived lung metastases (5/9, 56%) (P less than 0.05). In surgical/biopsy-derived tissues 9/9 colonic primaries were D14-positive, whereas only 1 of 6 lung primaries was positive (P = 0.002). We conclude that D14 and polyclonal anti-CEA both stain the majority of colon adenocarcinomas and that changes associated with prolonged fixation may reduce the positivity rate with both B18 and D14 monoclonal antibodies. All three antibodies stain autopsy-derived tissue from primary lung cancer to a significant degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Atypical membranous glomerulonephritis with fibrillar subepithelial deposits in a patient with malignant lymphoma.

A 61-year-old male treated for a malignant lymphoma developed a nephrotic syndrome. Renal biopsy revealed an atypical form of membranous glomerulonephritis whereby the epimembranous deposits were of fibrillar configuration. Immunoglobulin, kappa light chains and complement were demonstrated in a granular pattern. It is suggested that the fibrillar deposits represent an abnormal structural configuration of immune complex deposits.