Bone marrow biopsies of 674 patients with multiple myeloma (MM) were processed for diagnostic evaluation. Histologic variables were correlated with the clinical features to determine factors of value in predicting prognosis. Four of these were used to classify MM into six histologic types: Marschalko type; small cell type; cleaved type; polymorphous type; asynchronous type; and blastic type. These six types were subsequently combined into three prognostic grades: low, intermediate, and high, analogous to the malignant lymphomas. The quantity of plasma cell burden in the biopsy proved to be a useful criterion for histologic staging of MM, supplementing any clinical staging system in use. Both these parameters, grade and stage, provide information required for decisions on treatment modalities, while the effects of therapy can be monitored by sequential biopsies.

Summary:Recently CYFRA 21-1, a new tumour marker measuring a fragment of cytokeratin 19, was introduced (1,2) and proved to be suitable for the follow-up care and monitoring of the therapy of non-small cell lung carcinomas, especially squamous cell carcinomas of the lung (3, 4). Besides CYFRA 21-1, there are two other tumour markers available, called tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS), which also measure different cytokeratins in serum. In a retrospective study we investigated the clinical significance of these 3 cytokeratin markers in lung cancer compared with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). We investigated the sera of 50 healthy persons, 273 patients with various benign diseases and 218 patients with histologically proven lung cancer. In a first step the specificity versus benign diseases of the lung was established for all the markers, and was fixed at 95%. Then the single and combined sensitivities were calculated. CYFRA 21-1 proved to possess the highest sensitivity in lung cancer in general (61%), in non-small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas, neuron-specific enolase proved again to be the marker of first choice (55%). Combined determinations proved clearly increased sensitivity only for large cell carcinomas (CYFRA 21-1 + TPA: 77%) and for small cell lung carcinomas (CYFRA 21-1 + NSE: 62%). From our investigations it was evident that TPA detects at least partly the same substance as CYFRA 21-1 (the sensitivities compared with the markers TPS, CEA, SCC and NSE were rather high, but not as high as for CYFRA 21-1), whereas the TPS assay measures a completely different clinical chemical analyte (lowest number of true positive test results over the whole investigation). These findings correspond cleary to the very recent results of the comparison of CYFRA 21-1, TPA and TPS by immunoblotting (5). Introduction_ ,, , ^.r-r-,^ * ~ * Recently a new tumour marker, called CYFRA 21-1, In many industrialized countries, lung cancer is the was described for the detection of cytokeratin 19-inost common cancer in men and is climbing quickly fragments in serum (1, 2). Cytokeratins and other toward the same incidence in women. Clinical chem-intermediate filaments of the cell like vimentin and ical methods for the support of adequate follow up desmin have become well known since the developcare and the control of efficiency of therapy are avail-ment of monoclonal antibodies in histopathology for able only for small cell lung carcinomas, and they the differentiation and classification of physiological consist of the determination of neuron specific enolase and pathological tissues (8, 9). The expression of a (6, 7).single cytokeratin or a combination of certain cyto-

Bone marrow biopsies of 678 untreated patients with established malignant non-Hodgkin's lymphomas (ML) were investigated. The bone marrow was involved in 468 cases, an overall frequency of 69%. The Kiel classification of the ML (based on lymph node histology) was applied and the biopsies were classified: ML lymphocytic 36%, ML 'hairy cell' 24%, ML lymphoplasmacytic/cytoid 24%, ML centrocytic 6%, ML centroblastic/centrocytic 4%, ML lymphoblastic (without ALL) 3%, ML centroblastic 2% and ML immunoblastic 1%. The life tables of the patients were similar whether classified according to the histology of the lymph node or the bone marrow. A multivariate computer based analysis of both clinical and histological data was performed to test their prognostic relevance. The cell type, the proliferation pattern and the extent of infiltration in the bone marrow all proved to be factors of prognostic significance. The results indicate that classification of the ML based on lymph node histology is applicable to the bone marrow, is reproducible and has prognostic significance. Consequently, a bone marrow biopsy is a useful clinical tool for staging and for histological classification of patients with ML.

Summary: After the introduction (1, 2) and methodical evaluation (3, 4) of a new method for the quantitative measurement of the bone isoenzyme of alkaline phosphatase (test-combination bone alkaline phosphatase, Boehringer Mannheim), we started a retrospective clinical study for the follow-up investigations of breast cancer patients. Our aim was to establish the significance of the routinely used tumour markers, CEA and CA 15-3, in combination with bone alkaline phosphatase for the early detection of metastatic spread to the bone. We investigated 492 sera from 92 patients suffering from breast carcinoma, and we compared each date of investigation with the results of the clinical examination and with the results of medical imaging, if that had been performed. From a previous study involving skeleton scintigraphy (5) we knew that single examinations do not allow a differential diagnosis between benign and malignant disorders of the bone, so we based our calculations on differences between sequential investigations. We found that in follow-up investigations of patients with breast carcinoma the combined determination of CEA, CA 15-3 and bone alkaline phosphatase may be indicative for the localisation of metastatic disease. The determination of the bone alkaline phosphatase is easy to handle with a short assay time and good reproducibility; it can therefore be recommended. Introduction,. ,. ~ ^ ,. -earlier diagnosis of recurrent disease, they are not Breast cancer is still the most frequent malignant able to discriminate between the localization of the disease in women, with growing incidence and mor-metastatic spread. Knowing the low specificity and tality rates in Western countries. In the follow-up of sensitivity of skeleton scintigraphy for the early dethese tumour patients the early detection of relapse tection of bone metastases and the high risk of the or metastases is of great importance for successfull development of bone involvement in patients suffering treatment and therefore influences prognosis. The de-from breast carcinoma, it would be of great interest termination of tumour markers in serum, like CEA to determine whether the joint assay of bone alkaline and CA 15-3, is useless for screening or primary di-phosphatase

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