Michael Bergholz

Overwhelming infection after splenectomy in spite of some spleen remaining and splenosis. A case report.

SummaryA fatal case of overwhelming postsplenectomy pneumococcal sepsis is presented occurring in a 37-year-old female 11 years after removal of the spleen because of traumatic rupture. The patient died 11 h after admission to hospital and about 32 h after sudden onset of illness. At necropsy splenic tissue, splenosis, disseminated intravascular coagulation, and thrombi within the arterioles consisting of gram-positive cocci and adrenal hemorrhage were found. The clinical, laboratory, and postmortem findings are described. Reports had been published of 41 other cases of overwhelming postsplenectomy infection (OPSI) in patients aged 20 years ore more, but only three of these cases of OPSI syndrome occurred in spite of remaining splenic tissue. The longest interval between extirpation of spleen and subsequent sepsis was 42 years, indicating a small but lifelong risk of severe infection in asplenic patients. In view of the literature, the role of spleen in infection defence, the splenic function in blood clearance, and the prevention of postsplenectomy infections by antibiotical prophylaxis, pneumococcal vaccine, and reimplantation of autochthonous splenic tissue or infrared contact coagulation are discussed.

Heterogeneity of tumour necrosis factor production in renal cell carcinoma

Endogenous tumour necrosis factor (TNF) production was investigated by in situ hybridisation and immunohistochemistry in 8 renal cell carcinoma (RCC) patients at different stages of disease. Analysis of frozen sections of tumour biopsy specimens revealed variable degrees of macrophage infiltration and great heterogeneity in TNF gene expression. Two metastatic tumours investigated showed abundant TNF protein production and marked macrophage infiltration. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Two years after nephrectomy the individual survival time was recorded; however, the small numbers did not yet allow any correlation of TNF production to the clinical course of disease. Further studies will be required to eventually reveal the role of TNF in renal cell carcinoma development.

Clinical characteristics of high-grade lymphomas with immune genes in germline configuration

In a prospective study of 42 high‐grade lymphomas which were categorized according to the Kiel classification, the clinical significance of immune genotyping was studied. Immunoglobulin (Ig) and T‐cell receptor (TCR) gene rearrangements were investigated. In 33 cases the immune genotype confirmed the phenotype. In one case with equivocal phenotype a TCR β‐chain rearrangement proved the T‐cell origin of the lymphoma. None of the cases showed a bigenotype. There were eight lymphomas with immunoglobulin and TCR beta‐chain and gamma‐chain genes in germline configuration, which were divided into a group of immature lymphomas and a group of lymphomas with a more mature phenotype. The immature lymphomas had widespread disease, rapid progression, and favorable prognosis after intensive chemotherapy. The group of T‐cell and Ki‐1 lymphomas with null‐cell genotype was clinically heterogeneous. Three of four cases were secondary lymphomas after lymphomatoid papulosis, lymphomatoid granulomatosis, or Hodgkins disease. All cases presented with extranodal involvement. Only one of these patients is in continuous remission. In conclusion, the lack of immunoglobulin and TCR beta‐chain and gamma‐chain gene rearrangements does not exclude the diagnosis of high‐grade malignant lymphoma, especially in cases with unusual extranodal involvement. However, the DNA analysis identifies a null‐cell genotype subset of high‐grade lymphomas which may have clinical significance.

Krebsrisiko bei papillären Proliferationen der Brustdrüse

SummaryMorphological differentiation according to localization and degree of proliferation must precede any estimate of the probability of cancer occurring in patients suffering of papilloma. The most frequently occurring papillomas are those of the distal lacteal ducts (so-called lobular papillomas). These can only be seen microscopically and they are often multiple, but they do not essentially heighten the risk of cancer. There is, furthermore, no greater risk of cancer to be reckoned following local excision of a papilloma of the nipple, but one should be certain of total excision. Papillomas of the larger preponderant proximal ducts (so-called ductal papillomas) often show an increased rate of proliferation and occasionally display atypias. Although a multicentric occurrence cannot be generally presupposed, controls should be carried out constantly after local exstirpation. Proliferating papillomas can be overdiagnosed morphologically. In borderline cases with focal nuclear atypias, however, further surgical measures (subcutaneous mastectomy, if possible) should be discussed. Apart from morphological facts individual datas (biopsy in sano, radiological findings, age of the patient etc.) must be considered in this discussion.ZusammenfassungDer Abschätzung des Krebsrisikos für Papillompatienten muß eine morphologische Differenzierung der excidierten Gewächse nach Lokalisation und Proliferationsgrad zugrundeliegen. Die nur mikroskopisch erkennbaren Papillome der distalen Milchgänge (sog. lobuläre Papillome) kommen am häufigsten vor und treten oft multipel auf. Durch sie wird das Krebsriskio aber nicht wesentlich gesteigert. Nach Lokalexcision eines Papilloms der Brustwarze ist gleichfalls nicht mit einem erhöhten Krebsrisiko zu rechnen, doch die vollständige Entfernung sollte gesichert sein. Papillome größerer vorwiegend proximaler Milchgänge (sog. duktale Papillome) zeigen häufig eine gesteigerte Proliferationsaktivität und gelegentlich Atypien. Der Excision eines Gangpapilloms sollten daher regelmäßige Nachkontrollen immer folgen, auch wenn eine Multizentrizität nicht vorauszusetzen ist. Proliferierende Papillome können morphologisch überdiagnostiziert werden. In Grenzfällen mit focalen Kernatypien sollten aber weitere chirurgische Maßnahmen diskutiert werden (gegebenenfalls mit subcutaner Mastektomie). Hierbei müssen neben den morphologischen Gegebenheiten die falleigenen Daten (Biopsie in sano, radiologische Befunde, Alter der Patienten usw.) berücksichtigt werden.

Angioimmunoblastische Lymphadenopathie und persistierender Virusinfekt

SummaryThe presence of rubella virus antigen was demonstrated by means of immunohistological methods in two cases of angioimmunoblastic lymphadenopathy. One patient had elevated serum anti rubella titer and myocarditis. These findings support the idea that angioimmunoblastic lymphadenopathy develops as a combined effect of persistent virus infection and partial immune deficiency.ZusammenfassungMit immunhistologischen Methoden wurden in zwei Fällen von angioimmunoblastischer Lymphadenopathie Rötelnantigene in Lymphknoten nachgewiesen. Ein Patient hatte einen hohen Rötelnantikörpertiter und eine Myocarditis. Diese Befunde stützen die Vermutung, daß sich die angioimmunoblastische Lymphadenopathie aus einem Zusammenspiel von persistierendem Virusinfekt und partiellem Immundefekt entwickelt.The presence of rubella virus antigen was demonstrated by means of immunohistological methods in two cases of angioimmunoblastic lymphadenopathy. One patient had elevated serum anti rubella titer and myocarditis. These findings support the idea that angioimmunoblastic lymphadenopathy develops as a combined effect of persistent virus infection and partial immune deficiency.

Monoclonal Antibodies for Improved Evaluation of Breast Cancer Prognosis

Worldwide efforts are in progress to decide more accurately and also more related to the single case, whether curative breast conserving surgery should be favoured or not (FISHER et al. 1985, VERONESI et al. 1981, 1983). The overall results of studies in our opinion can be proved, when the decision for breast conserving surgery is not only oriented at the extension of a tumor, measured in centimeters, but also the biological parameters like local spread (degree of peritumoral lymph-angiosis carcinomatosa and tumor cell dissociation), grading, degree of invasion, proliferative activity, steroidreceptor equipment are taken into consideration (SCHAUER et al. 1985, 1986). In our country, when planning the two main National Breast Cancer Projects, breast conserving surgery in the pT1 N0M0 group on the one hand and mastectomy in pT2 cases, followed in this group by interdisciplinary radio- and chemotherapy, on the other hand, two different planning and performance groups took care of program development, and the same groups now closely work together in the performance of the programs.

Immunohistochemical studies of the determination of the hormone receptor status of breast cancer

Immunohistochemical examinations of 89 breast cancer specimens were performed using two different monoclonal antibodies. One marked the nuclear estrogen-receptor (ER) protein (anti-ER, Abbott), whereas the other marked an ER-related cytoplasmic protein (ER-D5 Amersham). Comparison of the results of the biochemical assay with those of the immunohistochemical markers revealed the following correlations: 75% anti ER and 71% ER-D5. Clinical follow-up studies are necessary to specify the relevance of these new immunohistochemical techniques in the anti-hormonal therapeutic management of breast cancer patients.SummaryImmunohistochemical examinations of 89 breast cancer specimens were performed using two different monoclonal antibodies. One marked the nuclear estrogen-receptor (ER) protein (anti-ER, Abbott), whereas the other marked an ER-related cytoplasmic protein (ER-D5 Amersham). Comparison of the results of the biochemical assay with those of the immunohistochemical markers revealed the following correlations: 75% anti ER and 71% ER-D5. Clinical follow-up studies are necessary to specify the relevance of these new immunohistochemical techniques in the anti-hormonal therapeutic management of breast cancer patients.

86. Morphologische Kriterien für die brusterhaltende Chirurgie

SummaryEfficiency of radiation therapy is dependent on the tumor mass on the one hand and on “radiosensitivity” on the other hand. Thus the locoregional acribic surgery is an urgently required presupposition regarding therapeutic success. In cases of early breast cancer (pT 1 NO MO) unfavorable prognostic factors may initiate a discussion on adjuvant therapy. From the curative point of view at present breast preserving surgery referring tumors bigger that 2 cm (pT 2) should be performed in cases with more advantagous prognostic parameters (low grade malignancy up to grade 11 a, low degree of tumor cell dissociation, favorable subtype, no relevant lymphangiosis carcinomatosa detectable, etc.). Additional immunohistochemical analysis of the receptor status and the proliferative compartment can be helpful for later therapeutic decisions. The possibility of breast preservation in only palliatively treated cases must be discussed separately.ZusammenfassungDa die Wirksamkeit der Strahlentherapie einerseits tumormassenabhängig ist und andererseits nicht der Biologie des Einzeltumors angepaßt ist, ist die akribische locoregionäre Chirurgie bei Brusterhaltung für den definitiven Therapieerfolg eine unabdingbare Voraussetzung. Auch beim „kleinen Mammacarcinom” (pT 1 NO MO) ist bei ungünstigen morphologisch und immunhistochemisch faßbaren Prognosefaktoren eine adjuvante Therapie diskutierbar. Die brusterhaltende Chirurgie bei Tumoren > 2 cm (pT 2) sollte aus kurativer Sicht nur bei Tumoren mit günstigeren biologischen Parametern (niedriger Malignitätsgrad-(Grad II a), niedriger Dissoziationsgrad, günstiger Subtypus, keine ausgeprägte Lymphangiosis carcinomatosa) erfolgen. Zusätzliche immunhistochemische Analyse des Receptorstatus und des proliferationsaktiven Compartments können für Entscheidungen auch bei späteren Zusatztherapien hilfreich sein. Die Möglichkeit der palliativen brusterhaltenden Chirurgie beim inkurablen Mammacarcinom bleibt dadurch unberührt.

Detection of Epstein-Barr Virus Genomes in Lymphoproliferative Diseases

Epstein-Barr virus (EBV), the etiologic agent of infectious mononucleosis, has a clearly established association with endemic Burkitt’s lymphoma (BL), nasopharyngeal carcinoma (NPC), and secondary B-cell proliferations in immunosuppressed individuals [1,2]. Epidemiologic studies have linked Hodgkin’s disease (HD), which accounts for 30–50% of malignant lymphomas in Western countries, to previous infectious mononucleosis [3]. Increased EBV-specific antibody titers were frequently observed in HD patients [4,6]. Recently, DNA filter hybridization studies pointed to an association of EBV with up to 20% of isolated cases of HD [7,9]. In EBV-positive HD cases studied in more detail, the viral DNA was monoclonal in origin and confined to Hodgkin and Reed-Sternberg (H and RS) cells that constitute the malignant cell population of HD [10,11]. However, since H and RS cells often account for less than 1% of the total cell number in HD-afflicted lymph nodes, it is possible that EBV escaped detection by filter hybridization methods in many HD cases. Therefore, we screened 198 HD cases, 151 non-Hodgkin lymphomas (NHL), and 34 non-malignant lymph node biopsies, all of which were clinically unrelated to HIV-infection, with the highly sensitive polymerase chain reaction (PCR) [12].