Baruch Klein

Splenomegaly and solitary spleen metastasis in solid tumors

Metastasis to the spleen from various neoplasms is very rare. Most of the splenic metastases are found at autopsy, and are part of a widespread disease. Four patients had cervical cancer (1 patient), endometrial cancer (1 patient), lung carcinoma (1 patient), and malignant melanoma (1 patient). All patients had splenic involvement without pathologic evidence of lymph node metastasis, and all underwent splenectomy. Three of the four presented with painful splenomegaly. The time from diagnosis to the development of splenic metastasis varied from 20 to 24 months. Two of the four patients had postoperative radiotherapy, one patient received intraperitoneal chemotherapy, and the patient with the melanoma received adjuvant chemotherapy. The rarity of solitary spleen metastasis from solid tumors and the treatment modalities are discussed.

Involvement of the central nervous system by ovarian carcinoma

Ovarian carcinoma rarely metastasizes to the central nervous system (CNS). Of 110 patients with epithelial ovarian carcinoma treated at the Northern Israel Oncology Center between the years 1979 and 1985, only five (4.5%) had CNS involvement. The median age of the patients was 54.5 years. All of them had treatment with cisplatin and Adriamycin (doxorubicin). The median duration from diagnosis to the development of brain involvement was 17 months. The median survival time was 28 months from diagnosis of carcinoma and 2 months from diagnosis of CNS disease. The increased incidence of this kind of metastasis in patients achieving local control of their advanced disease suggests that a change in the pattern of metastatic spread or the prolonged survival permits occult CNS metastases to become apparent. A routine computerized axial tomography (CAT) scan of the brain should therefore be performed on patients with ovarian carcinoma with prolonged survival.

CORRELATION BETWEEN TUMOUR AND SERUM β2m EXPRESSION IN PATIENTS WITH BREAST CANCER

HLA class I antigens are composed of a major histocompatibility complex (MHC) encoded heavy chain that is associated non‐covalently with a light chain β‐2 microglobulin (β‐2m). When the HLA complex is metabolized, β‐2m is shed into the serum. A large variety of human and experimental tumours have altered MHC class I expression. In a previous study we observed elevated mean β‐2m serum levels in breast cancer patients, as compared to controls. To study the relationship between tumour expression and serum levels, we examined 54 patients with breast cancer. Tumour β‐2m was determined by immunohistochemistry and serum levels by the ELISA technique. Of the 54 patients, 38 had low and 16 had high β‐2m expression on the tumour. There was a significant correlation between tumour β‐2m and serum β‐2m levels (P= 0.02), with patients whose tumours expressed high β‐2m having high serum β‐2m levels. There was an inverse correlation between tumour grade and tumour β‐2m expression which approached statistical significance (P= 0.06). These findings suggest that in a substantial number of patients the high serum levels derive from shedding of β‐2m from tumour cells. These levels may have implications for tumour growth and metastases due to influences on immunological responses.

Satellitism of Platelets to Monocytes.

Satellitism of platelets to monocytes was observed in 3 patients suffering from polycythaemia vera, a myeloproliferative disorder and chronic lymphocytic leukaemia. This phenomenon occurred on cells in the buffy coat obtained from venous blood anticoagulated with heparin. The existence of platelet satellitism was reported to occur mainly to polymorphonuclears, but the present observation, as well as a previous report from our department, indicated that it may also exist to monocytes. Satellitism was achieved either by adherence of the platelets to monocytes, giving the impression of rosette formation, or by fusion of platelet pseudopodia with the monocyte membrane. The importance of this phenomenon in the evaluation of the platelet count using automatic instruments is discussed.

Lymph Node Revealing Solution: A New Method for Detection of Minute Axillary Lymph Nodes in Breast Cancer Specimens

The staging and prognosis of patients with breast cancer is related to the presence or absence of axillary lymph node involvement. However, in some cases no lymph nodes or too small a number of lymph nodes are revealed by the traditional method of palpating and sectioning the axillary fat. In the present study we demonstrate the usefulness of the lymph node revealing solution (LNRS) in breast cancer. Specimens from 13 patients, in whom <10 lymph nodes were identified in the axilla by the traditional method, were included in the study. After excising the lymph nodes by the traditional method, axillary tissue was immersed in LNRS for 6-12 hours. Additional lymph nodes, which stood out as white chalky nodules, were excised and processed as usual. The LNRS increased the mean number of nodes per case from 6.0+/-2.5 found by the traditional method to 12.54+/-4.61 nodes per case (p < 0.01). The size of the nodes identified by the LNRS was significantly smaller (p < 0.01) than those detected by the traditional method. The LNRS changed the lymph node stage of the disease in four of the studied cases (30%). LNRS seems to be the technique of choice for detection of axillary lymph nodes in cases where the number of detected lymph nodes by the traditional method is too small for accurate staging.

Deleted in Colorectal Cancer Protein Expression as a Possible Predictor of Response to Adjuvant Chemotherapy in Colorectal Cancer Patients

PURPOSE:The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy.METHODS:The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated.RESULTS:Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC−; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO−) only 54 percent are alive (P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO− survival rate was 75 percent and disease-free survival rate 62 percent (P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO− both dropped to zero (P = 0.0002). On the other hand, in the DCC− tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC−/CHEMO− had 57 percent survival; DCC−/CHEMO+ had 52 percent survival).CONCLUSIONS:DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC− tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC− patients.

Place of death of cancer patients in Israel: the experience of a 'home-care programme'

This is an analysis of the eventual place of death of 58 patients with advanced cancer, all of whom died over the course of one year following treatment at home by a home-care programme in an Israeli community. Seventeen (29%) died in their homes, 23 (40%) died in general hospitals and 18 (31 %) died in chronic hospitals. The correlation between place of death and the following factors was examined: the relationship between each patient and his primary care person (PCP), length of treatment by the home-care programme, age, sex, ethnic origin, degree of mobility at commencement of home care and principal symptoms. Only the degree of family relationship of the PCP showed significant correlation with the actual place of death of patients, whether at home or in hospital (p=0.03). None of the patients with a PCP of second-degree relationship died at home. The authors conclude that when the PCP is closely related to the patient and is accompanied by a home-care team trained to offer comprehensive assistance, two-thirds of the patients in an Israeli community could be spared chronic hospitalization and almost half of these could also eventually die at home.

A clinical evaluation of nuclear estrogen receptors combined with cytosolic estrogen and progesterone receptors in breast cancer

Breast cancer tissue from 95 women was simultaneously assayed for three receptors: cytosolic estrogen (CER), cytosolic progesterone (CPR), and nuclear estrogen (NER). The main objective was to determine whether the addition of NER assay to the currently accepted practice with only CER and CPR could improve the predictive capacity of receptors. Forty‐two patients were studied for response to hormone therapy and 95 patients were studied for survival; the median follow‐up period was 73 months (range, 8 to 300 months). The incidence of CER+, CPR+, and NER+ was 74%, 70%, and 52%, respectively. Each receptor appeared more frequently, although not significantly so, in higher age groups. Forty percent of tumors had all three receptors positive and 14% had all negative; the remaining tumors showed all possible combinations of receptors. Both the rate of response and survival curves among 70 patients with CER+ did not show any significant difference whether NER was positive or negative. Also, among 38 patients with CER+, CPR+, and NER+, there was no significant difference in the clinical outcome as compared to 17 patients with CER+, CPR+, and NER‐. Among 25 patients with CER‐ the rare occurrence of NER+ in only three patients did not suggest any clinical implication. It is concluded, therefore, that on overall clinical grounds the current series does not support the addition of NER assay whenever data is available on both CER and CPR.

Soluble histocompatibility antigen class I in breast cancer patients in relation to tumor burden

Serum beta‐2 microglobulin (B‐2M) levels were studied in 365 breast cancer patients and 210 age‐matched controls. The patients were divided into three groups: Group A, new patients at diagnosis; Group B, patients at follow‐up; and Group C, metastatic patients. The mean B‐2M of all breast cancer patients plus or minus one standard deviation (3.5 ± 1.2; range, 1.1 to 5.9) was significantly higher than normal controls (1.29 ± 0.49; range, 0.3 to 2.3; P < 0.005). When the three patient groups were compared with each other, the mean B‐2M level of Group A (3.0 ± 1.5; range, 0.9 to 6.9) was similar to that of Group C (4.22 ± 1.1; range, 2.0 to 6.4). The mean B‐2M of both Groups A and C was significantly higher than that of Group B (2.38 ± 1.02, range, 0.4 to 5.4; P < 0.001). In Group A the mean B‐2M decreased significantly after a 12‐month period and reached the mean level of Group B but not that of normal controls. When patients in Group B were analyzed by their stage of disease at diagnosis, there was no significant difference between Stages I and II. There was a significant difference in the mean B‐2M levels between Stages I and III. In relapsing patients, mean B‐2M levels increased. These findings suggest that serum B‐2M levels may reflect tumor burden, and even in patients at follow‐up, occult tumor cells may activate the immune system.

Two abnormal clones in the bone marrow cells of a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be a clonal disorder, although most investigations have failed to show chromosomal abnormalities. The present patient suffered from PNH and exhibited in bone marrow cells two abnormal clones with 47 chromosomes in addition to cells with 46 chromosomes. One clone showed trisomy 9, a finding previously reported in leukemias and myeloproliferative disorders. Thus, PNH seems to be a clonal myeloproliferative disease.