[Diagnosis and immunohistochemistry of medullary breast cancer]. / Diagnostik und Immunhistochemie des medullären Mammakarzinoms.

Medullary carcinoma of the breast has a relatively favorable prognosis despite its malignant histopathological appearance, providing a challenge for the pathologically based diagnosis of breast cancer. Macroscopic and microscopic findings combined provide diagnostic criteria. The importance of the immunophenotype of medullary carcinoma is not well defined. Because the reproducibility of morphological criteria is limited, we conducted an immunohistochemical study in search of markers that could facilitate histopathological classification. We examined 32 medullary carcinomas in comparison with 30 high grade ductal invasive carcinomas with similar morphology using 23 different immunohistochemical markers. The results showed an overlap with the so called basal like subtype of invasive breast cancer (negativity for steroid hormone receptor, positivity for basal cytokeratins). None of the immunohistochemical markers enabled a specific discrimination between the two groups. Medullary carcinomas overexpress EGF-R more frequently (P<0.004). In combining the characteristic morphological criteria and the immunohistochemical detection of the basal like phenotype and EGFR, a higher diagnostic accuracy can be achieved. The immunophenotype alone does not allow a definite classification of medullary carcinoma.

[Histopathology of leukaemic non-Hodgkin's lymphoma in bone marrow]. / Histopathologie leukämischer Non-Hodgkin-Lymphome in Knochenmark.

Staging biopsies of the bone marrow in lymphoma patients are among the most important indications and therefore of substantial practical importance. Occasionally it is the only organ infiltrated, and therefore a bone marrow biopsy is the prime diagnostic choice in cases of leukemic lymphomas. A synoptical diagnostic approach relying on immunophenotypic as well as on molecular biological criteria aside from histomorphology (cytomorphology), is of utmost importance for the subtyping of malignant lymphomas. This too can be done reliably on bone marrow biopsies, as comparative studies have yielded a concordance rate of more than 90% with lymphoma typing on corresponding lymph nodes. Cytology and the pattern of infiltrates, (i.e. diffuse, interstitial, nodular peritrabecular and intrasinusoidal), in combination with immunological phenotyping are the mainstays for subtyping, giving clear-cut decisions in most cases of small B-cell lymphoma, mantle zone as well as marginal cell and follicular lymphomas and hairy cell leukemia. Among the blastic variants the most important are the lymphoblastic lymphomas of either B- or T-cell type which have to be discerned from AML and the so-called blastoid mantle cell lymphomas. T-cell lymphomas are rare compared to B-cell lymphomas. Among the rarely seen T-cell neoplasias the lymphoma of large granular lymphocytes is the dominating lymphoma, which in most cases can only be diagnosed reliably by molecular biological means, followed by T-CLL, Sezary's syndrome and hepatosplenic chi delta lymphoma.

Short-term culturing influences the number of bcr/abl-fused cells detected by fluorescence in situ hybridisation in bone marrow aspirates of CML patients.

Fluorescence in situ hybridisation (FISH) has been proven as a helpful tool in diagnosis and monitoring of bcr/abl fusion in chronic myelogeneous leukaemia (CML). Since long-term cultures are known to decrease the number of bcr/abl-fused cells, it is questionable whether similar effects are detectable in short-term cultures, a technique often preceding FISH analysis. Therefore, we evaluated bone marrow aspirates of 10 CML patients at biopsy and after culturing for between 24 and 144 h by FISH. The percentage of bcr/abl-fused cells in FISH varied between 15 and 70% at biopsy. In samples with 15 and 30% of aberrant cells at biopsy, an increase of about 20% per day was seen within the first 48 h. In longer lasting cultures, the percentage of leukaemic cells then asymptotically approached a value of 60-70%. In patients with 38 and 50% of bcr/abl-fused cells at biopsy, an increase of about 20% could be detected in the first 24 h. Then 65-70% of the cells already bore the bcr/abl fusion, and the percentage of leukaemic cells was almost constant for longer lasting cultures up to 144 h. In patients with a percentage of about 70% before culturing, no increase in positive cells was detected. These results emphasize the impact of short-term culturing on the number of bcr/abl-fused cells. In particular, the importance for monitoring CML patients is obvious. Therefore the effect described should be taken into account in order to avoid misinterpretation and incorrect therapy decisions in CML patients.