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Background: Lymph-node diagnostics is performed using thin sections, with help of immunohistochemistry by light microscopy and supplemented by molecular pathology., Objectives: Which are the scientific and diagnostic perspectives of 3D and 4D lymph node investigations, using laser, scanning, and computer technologies? What is the impact of machine learning in complex data analysis., Results: It was shown in different investigations that the analysis in space and time (3D/4D) of lymph node tissue is able to provide a lot of new information concerning biology and diagnostics and enable excellent evaluations applying machine learning., Conclusion or Discussion: 3D and 4D analysis of human lymphoid tissue gives new insights into immunologic mechanisms and malignant lymphomas., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The human body comprises around 600 lymph nodes as constituents of a decentralized and dispersed immune system. The main task of lymph nodes is cleaning the lymph fluid and defending the organism against outer and inner threats by bacteria, viruses and tumour cells. The histologic picture of lymph nodes reflects the different strategies of the innate and adaptive immune system, which allocates antigen presenting cells, macrophages, B‑ and T‑cell systems and reticulum cells. However, the histological picture, without any additional investigations, usually only allows speculation about the causative agent like toxoplasmosis, other bacteria or viruses. This chapter describes different lymph node reactions in detail in order to obtain a better understanding of specific immune reactions allowing a precise diagnosis and a reliable distinction from malignant processes. The last issue in particular is one of the main tasks of haematopathology. In addition to these known principles, we try to integrate results obtained with the new method of three-dimensional (3D) microscopy of fixed lymphoid tissue. At first glance, this seems to be unusual. Nevertheless, we try to apply this approach, since 3D visualization of morphological details provides distinct cellular details as well as new interpretations of cell-cell interactions and the functions of lymphoid compartments, like germinal centres and T‑zones., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

After 8 years, the WHO has now published the updated version of the 4th edition of the classification of hematopoietic and lymphoid tumors. This update provides a conceptual rewrite of existing entities as well as some new provisional entities and categories, particularly among the aggressive B‑cell lymphomas. Important new diagnostic categories include the high-grade B‑cell lymphomas, the large B‑cell lymphoma with IRF4 rearrangement, and the Burkitt-like lymphoma with 11q aberrations. Of particular importance, new concepts concerning the taxonomy and classification of early lymphoid lesions or precursor lesions are included, such as the in situ follicular neoplasia or the in situ mantle cell neoplasia. In addition, the concept of indolent lymphoproliferations, such as breast-implant-associated anaplastic large cell lymphoma and the indolent T‑cell lymphoproliferative disorder of the gastrointestinal tract, has been strengthened. Finally, diagnostic criteria for existing lymphoma entities have been refined.

The update of the 4th edition of the WHO classification for hematopoietic neoplasms introduces changes in the field of mature aggressive B‑cell lymphomas that are relevant to diagnostic pathologists. In daily practice, the question arises of which analysis should be performed when diagnosing the most common lymphoma entity, diffuse large B‑cell lymphoma. We discuss the importance of the cell of origin, the analysis of MYC translocations, and the delineation of the new WHO entities of high-grade B‑cell lymphomas.

The present article gives an overview of novel developments in the diagnosis of nodular lymphocyte predominant Hodgkin's lymphoma with reference to the revised WHO classification from 2016. Differential diagnoses that are discussed are progressively transformed germinal centers, T cell/histiocyte-rich large B cell lymphoma as well as transformation into a diffuse large B cell lymphoma.

Three paratracheal lymph nodes of a 20-year-old patient were submitted for examination, of which one showed numerous thyrocytes with large void nuclei and was suspected of being metastatic papillary thyroid carcinoma. The simultaneously resected thyroid gland, which was subsequently submitted showed findings consistent with Hashimoto's autoimmune thyroiditis (AIT). In the context of the resected goiter tissue, the suspected lymph node metastasis was identified as a hyperplastic ectopic (so-called parasitic) goiter nodule with thyrocytic changes typically seen in Hashimoto's AIT, such as oxyphilic cell alterations and a high plasma cell content. The re-examination of the suspicious lymph node revealed complete lack of a marginal sinus, thus excluding the diagnosis of a lymph node as well as the diagnosis of thyroid carcinoma metastasis.

Background: The detection of characteristic genomic aberrations by fluorescence in situ hybridization (FISH) has a high diagnostic impact on lymphomas according to the World Health Organization (WHO). To investigate the reproducibility of non-isotopic ISH results a multicenter trial was carried out involving eight institutes for hematopathology., Material and Methods: Analyses were performed on two diffuse large B-cell lymphomas (DLBCL) without known aberrations, on one follicular lymphoma with a IGH/BCL2 translocation and BCL6 split and on two B-cell lymphomas intermediate between DLBCL and Burkitt's lymphoma with c-MYC and BCL2 rearrangements, one with an additional BCL6 split. Break-apart probes for BCL6 and c-MYC, as well as fusion probes for the c-MYC/IGH and the IGH/BCL2 translocations were used., Results: All aberrations were correctly detected by all centres and no false positive or false negative results were obtained. The numbers of positive cells varied from 25% to 94%. Pearson's correlation coefficient between the centres was always > 0.8., Conclusions: The ISH analysis of recurrent genomic aberrations in formalin-fixed paraffin-embedded (FFPE) tissue is a highly reproducible technique which yields substantial additive help for lymphoma diagnostics.

Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. The histological patterns of NLPHL variants are characterized by different localizations of the tumor cells, intranodular and perinodular and by the varying composition of the microenvironment. T-cell/histiocyte-rich B-cell lymphoma may be the result of an aggressive transformation of NLPHL. Classical lymphocyte-rich Hodgkin's lymphoma can usually be clearly distinguished from NLPHL by the immunophenotype of the tumor cells. Further differential diagnoses include follicular lymphoma and the follicular variant of peripheral T-cell lymphoma. Angioimmunoblastic T-cell lymphoma with CD20-positive blasts represents a differential diagnosis to the diffuse variants of NLPHL.

Immune suppression is a risk factor for malignant lymphoma development. Progress in medical science has increased the numbers of immunosuppressed patients due to organ transplantations or successful treatment of autoimmune diseases. Different forms of immune suppression and the respective lymphoma entities are discussed in this article. Another issue treated are gray zone lymphomas between Hodgkin's lymphoma and diffuse large B cell lymphoma. This category not only represents a diagnostic challenge but also represents more a true biological continuum.

Malignant lymphomas are classified into different entities according to their morphology, immunohistochemical parameters and clinical behavior. Several important pathogenetic events can be assigned to certain lymphoma entity types. Nevertheless, some cases present overlapping morphologic and immunohistochemical characteristics and a clear-cut diagnosis cannot be made. This is particularly the case with aggressive lymphomas for which a clear distinction cannot be made between the entities of diffuse large cell lymphoma/Burkitt lymphoma or primary mediastinal B cell lymphoma/classic Hodgkin's lymphoma. In order to redress this situation, two new gray zone entities were introduced in the WHO 2008 classification. Until further knowledge regarding the therapy, behavior and prognosis of these gray zone lymphomas has been gained, they should continue to be considered as distinct entities.

Hodgkin lymphoma (HL) is the most frequent nodal lymphoma in Europe. The B-cell derived Hodgkin-Reed Sternberg (HRS) cells are nearly completely deficient for expression of B-cell markers. Epstein-Barr virus (EBV) can be detected in about 40% of HL cases. Presumably, EBV protects HRS cell precursors from apoptosis. Histologically only single HRS cells are dispersed in a broad reactive cellular background. Interactions between HRS cells and their surrounding cellular infiltrate, among them paracrine activation of several signalling pathways, is crucial in HL. HRS cells also show autocrine activation of several signalling pathways. Among these, the aberrant expression and activation of seven different receptor tyrosine kinases (RTK) is of special interest, as many different antibodies and low molecular substances which inhibit RTK activity are already in clinical use for anticancer therapy. Therefore, blocking of RTK activities in HL may be a novel therapeutic option.

Purpose: The purpose of this study was to evaluate the safety and clinical value of MR-guided biopsies in an open 0.2 T low-field system., Materials and Methods: A total of 322 patients with suspicious lesions of different body regions were biopsied in a low-field MRI system (0.2 T, Concerto, Siemens). The procedures were guided using T 1-weighted Flash sequences (TR/TE = 100/9; 70 degrees). The lesions were repeatedly biopsied using the coaxial technique with a 15-gauge (diameter 2 mm) puncture needle. Complications and biopsy findings were analyzed retrospectively., Results: In all cases the biopsy procedures were successfully performed with MR guidance. In 298 patients diagnosis was able to be confirmed on the basis of the probes. The clinical follow-up showed that in 24 patients the lesions were missed by MR-guided biopsy. From this a sensitivity of 86%, a specificity of 87% and an accuracy of 93% were calculated. In two patients major complications were observed (morbidity rate 0.6 %)., Conclusion: MR-guided biopsy can be performed safely and precisely in a low-field MR system and are a supplement to US or CT-guided biopsies.

Diagnostic lymph node pathology is primarily focused on identification, definition and classification of lymphoid neoplasms. Less attention is paid to reactive lymph node changes as their causes often cannot be elucidated. We outline several particular types of lymph node reactions that allow a delineation of potential causative agents. A thorough understanding of the morphology of reactive lymph node changes can also aid in the differential diagnosis between reactive and neoplastic lymph node changes.

For the first time we describe a sclerosing mesenteritis that appeared acutely after abdominal operations. The patient suffered from diffuse abdominal symptoms. There was a hard tumour in the left middle and lower abdomen. Histological analysis revealed fibrosis and bone tissue. Symptoms improved after application of prednisone and high-calorie infusions.

To identify pathogenetic mechanisms in Hodgkin lymphoma (HL) we performed global gene expression profiling of four HL derived cell lines and compared the expression profiles with those of normal B cells and B cell non-HL. This analysis revealed a global loss of B-cell specific gene expression in Hodgkin-Reed/Sternberg (HRS) cells (21). Further analysis showed that ABF-1 and Id2, which are both negative regulators of the B cell master transcription factor E2A and likely also Pax-5, are aberrantly expressed in HRS cell lines (11, 17). For Id2, immunohistochemistry showed expression in the HRS cells of all cases, and E2A could be coimmunoprecipitated with Id2 from HRS cell lines, indicating that the aberrant Id2 expression may indeed contribute to the loss of the B-cell specific gene expression in HL (17). An analysis of the global gene expression data for aberrant expression of genes which are frequently involved in neoplastic transformation identified six receptor tyrosine kinases (RTK) aberrantly expressed in HRS cell lines. All RTKs were also (co)-expressed in primary cases and mostly activated by auto- or paracrine mechanisms (18). Analysis of greater number of cases identified a subgroup of HL which encompasses about 20 % of cases characterised by coexpression of at least four of the RTKs. An survey of several B cell lymphoma types with a pan-phospho-tyrosine specific antibody indicated that mediastinal large B-cell lymphoma is beside HL the only entity where aberrant TK activities cause an aberrantly high cellular phospho-tyrosine content in a significant fraction of cases.

Hodgkin's lymphoma can be divided with the help of morphologic and immunohistochemical techniques into classical and nodular lymphocyte predominant Hodgkin's lymphoma. By single cell analyses it could be established that the tumor cells of Hodgkin's lymphoma are clonal B-cells with germinal center origin. In rare cases (less than 5 %), the Hodgkin and Reed Sternberg cells represent clonal tumor cells that derive from T-cells. By gene expression analyses it can be shown that Hodgkin cell lines represent an entity independently of their B- or T-cell-origin. Hodgkin cell lines show similarities to EBV transformed B-cells and in vitro activated B-cells. The genes found with the help of gene expression analyses may have crucial importance in the pathogenesis and are potentially new diagnostic markers and therapeutic targets.

The current WHO classification of Hodgkin's lymphoma (HL) generally distinguishes the relatively rare variant (approximately 5% of all cases of HL) of nodular lymphocyte predominant type from a second group, which comprises classical HL and is separated into four subtypes: lymphocyte rich type, nodular sclerosis type, mixed cellularity type and lymphocyte depleted type. The classical lymphocyte rich subtype is a new entity and based on the typical morphology, can be recognized by definition only by the immunohistochemical characteristics of the Hodgkin and Reed/Sternberg cells (HRS) (CD30+, CD15+, CD20-). Molecular single cell studies are consistent with the dichotomy of HL in nodular lymphocyte predominant and classical types and stress the exceptional position of the former, which shows similarities with non-Hodgkin's lymphomas in several aspects. On the molecular biology level the tumor cells of all kinds of HL turn out to be clonal B cells derived from germinal center cells. However, tumor cells of nodular lymphocyte predominant HL differ from those of classical HL by the pattern of somatic mutations. Considering the inability of HRS cells of classical HL to express a B cell receptor, they should perish under normal conditions. However, they escape from apoptosis by mechanisms so far only partially understood, such as genomic mutations of the l-kappa B gene and the fas receptor gene or probably by down-regulation of B cell markers. In rare cases, HRS cells of HL can also be derived from T cells, as could be demonstrated by single cell analysis. Also, it could be shown by single cell PCR that HL and non-Hodgkin's lymphoma of both B and T cell types can arise from a common precursor. These results suggest that future classifications of HL will not only take into account the morphological and phenotypical profile, but also mechanisms of transformation yet to be discovered.

This case report refers to two patients with the rare entity of an extraneural metastasizing central nervous system tumor. The first patient presented with ipsilateral cervical lymph node metastases 4 years after a diagnostic biopsy and 2 years after removal of an anaplastic oligodendroglioma, respectively. The origin of the metastases was confirmed by immunohistochemistry. The second case described was found in a 26-year-old female who had suffered from a spinal cord pilocytic astrocytoma in infancy and been treated by surgery and radiotherapy. On postmortem examination, transformation to a primitive neuroectodermal tumor was found. Morphological and immunohistochemical features of the metastases were exactly identical with those of the primary tumors in both cases. The pathomechanisms of metastasizing CNS tumors are discussed with reference to the reasons why such cases are so rarely observed. The incidence of remote metastases and differences depending on tumor type are estimated. No relation to malignancy grade can be detected.

Previous studies have concentrated on the proliferative behaviour of the neoplastic cell compartment in Hodgkin's disease (HD). The aim of the current investigation was to analyse the frequency of programmed cell deaths in Hodgkin and Reed-Sternberg (HRS) cells in the different subtypes of HD and to correlate this phenomenon with the expression of the bcl-2 oncogene. For this purpose, we investigated paraffin-embedded material from 63 cases of HD. Oncogene expression was determined by immunohistochemistry with the monoclonal antibody bcl-2-124. The detection of apoptotic cells was facilitated by application of the in situ end-labelling (ISEL) technique. Our results confirmed that bcl-2 expression is low in the lymphocyte-predominant subtype of HD. Apoptotic cells were found in all subtypes to a variable extent and were not significantly associated with any particular subtype. Interestingly, there was no correlation of bcl-2 expression and the presence or absence of apoptotic HRS cells. Hence, other factors must be operative in the regulation of programmed cell death in HD. Such mechanisms have been described for lymphocytes under various conditions, such as negative selection in germinal centres and within the thymus, DNA damage due to irradiation, and cellular cytotoxicity.

Hodgkin's disease, especially its biology and pathogenesis, has been under discussion for more than 160 years. Numerous investigations have focused on the nature and clonality of Hodgkin cells, but so far no definitive answer have been yielded by immunohistochemistry, Southern blotting and PCR. However, the use of single-cell PCR has now made it possible to answer the question of the derivation of Hodgkin cells. Using a micromanipulator, Hodgkin cells can be picked out of histological sections and B-cell specific gene rearrangements (VDJ) can be amplified. With this technique it has proved possible to demonstrate the B-cell derivation of Hodgkin cells and their clonality. Mutated immunoglobulin genes in lymphocyte-predominant Hodgkin's disease indicate a germinal center cell origin of Hodgkin cells of this type. These findings, however, do not exclude cases of Hodgkin's disease with Hodgkin cells with a T-cell genotype.

The diagnosis of lymph node lesions frequently requires the employment of additional studies. Lineage and clonality can be regarded as the most crucial diagnostic parameters. In some cases the diagnosis remains ambiguous even after immunohistochemistry and molecular biologic techniques have to be applied. These molecular biologic techniques are based on specific rearrangements of the immune genes that occur during T- and B-cell development. Whereas Southern blotting has become a standardized and reliable means for the detection of lineage and clonality, the limited availability of fresh frozen material frequently restricts its clinical applicability. The polymerase chain reaction has facilitated the investigation of immune gene rearrangements in formalin-fixed and paraffin-embedded tissue samples. This communication reviews the recent developments in this field.

Plasma cellular osteomyelitis was seen in the metaphysis while sclerosing osteomyelitis affected the diaphysis of long bones. In only about 20% of both forms local bacteria were noted. The onset of symptoms was inconspicuous and both clinical and radiological signs were nonspecific. Curettment or resection usually cured the disease. In some cases, however, aggressive surgery was necessary. As to surgery and outcome sclerosing osteomyelitis appeared less riskful than plasma cellular osteomyelitis. Both forms apparently represent the same basic pathological condition.

A polymerase chain reaction based method was established using immunoglobulin VH and VK gene rearrangements as markers to detect clonal B cell populations in paraffin embedded sections. Family specific VH and VK primers are used in separate reactions together with the corresponding J primers to amplify rearranged VH and VK genes from genomic DNA. This allows to distinguish clonal from polyclonal B cell populations in most of the cases. The method may be helpful in routine diagnosis of B cell NHL and some morphological and immunohistochemical difficult cases.

Extranodal lymphomas of the thyroid (n = 19), kidney (n = 15) and testis (n = 30) were investigated histologically and immunohistochemically using the monoclonal antibody Ki-FDC1P, which recognizes follicular dendritic cells on paraffin sections. Only lymphomas of the thyroid were of MALT-lymphoma type and contained tumor associated abortive follicles of follicular dendritic cells. In kidney and testis, no MALT-Lymphomas were found. Lymphoepithelial lesions, a hallmark of MALT-Lymphomas, occurred not only in thyroid MALT-lymphomas, but also in testicular centroblastic lymphomas (lacking other features of MALT-lymphomas). Therefore, lymphoepithelial lesions are not specific for MALT-lymphomas.

We have investigated seven cases of large cell lymphomas (LCL) developing simultaneously or metachronously to nodular lymphocyte-predominant Hodgkin's disease (nodular paragranuloma, NP) for the presence of EBV and the chromosomal translocation t(14;18) by use of the polymerase chain reaction (PCR). The expression of the bcl-2 oncogene product in these cases and in five cases of progressive transformation of germinal centres as a potential precursor of NP was detected immunohistochemically with the monoclonal antibodies bcl-2-100 and bcl-2-124. All cases investigated were negative for EBV genomic material. The chromosomal translocation t(14;18) was also absent. Expression of the bcl-2 oncogene could be detected only in one case of nodular paragranuloma and in an unrelated case of LCL. Hence, LCL developing out of NP differ from other germinal center derived high-grade lymphomas.

In the literature EBV is considered a possible etiologic factor for Hodgkin's disease (HD). We investigated 187 cases of HD for the presence of Epstein Barr virus using the polymerase chain reaction (PCR) technique on formalin fixed, paraffin embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. The 187 cases included all subtypes. 66 cases (35.2%) were positive for EBV DNA. The statistical analysis of follow-up data from 130 patients revealed no influence of EBV DNA on survival time. In our investigation detection of EBV DNA by PCR showed no prognostic relevance for patients with HD.

Studies demonstrating Epstein-Barr virus (EBV) DNA in Hodgkin's disease (HD) provide little information about the EBV-status in the lymphocyte predominant subtype (nodular paragranuloma) which is due to the small number of cases investigated. Therefore we studied 99 typical cases of nodular paragranuloma for the presence of EBV-DNA using the polymerase chain reaction (PCR) technique. Genomic DNA was amplifiable in 71 cases; 29 cases (= 40%) were positive for EBV-DNA (EBNA-1). In situ hybridization revealed EBV-RNA (EBER-1) in L&H cells and in a few lymphocytes. PCR results were correlated to clinical follow-up data and did not show any statistically significant relationship between EBV positivity and survival of the patients.

This investigation characterizes the proliferating cells in Hodgkin's disease. We used the antibody PC 10 which reacts with the proliferating cell nuclear antigen (PCNA) and works on paraffin sections in combination with B- and T-cell markers in a double-staining technique. In all 38 cases of Hodgkin's disease (lymphocyte predominant type n = 10, nodular sclerosis type n = 10, mixed cellularity type n = 10, lymphocyte depletion type n = 8) a high percentage of the Hodgkin and Sternberg-Reed cells (95%-97%) expressed PCNA. There was no statistical significance between the different types. In contrast, only a small amount of the reactive lymphocytes (2.8%-3.4%) demonstrated positivity for PCNA in the four types of Hodgkin's disease. Nearly all of these lymphocytes were T-lymphocytes.

Since 26 years Hodgkins disease is classified according to the Rye classification into 4 types. This classification is based on morphology and has turned out to be clinically relevant. However, sometimes the classification on morphological and immunohistochemical ground can be difficult to put a special case in a defined category of the 4 types. In addition, there seems to be no sharp, or well defined borders between Hodgkin's disease and Non-Hodgkin's lymphomas, especially T-cell lymphomas. Immunophenotyping of small lymphocytes and detection of follicular dendritic cells can demonstrate typical patterns in different types of Hodgkin's disease. In all types of Hodgkin's disease there is the same amount of proliferating small T-cells present. Hodgkin cells are lymphoid cells with B- or T-cell markers. Hodgkin cells of nodular para-granuloma (lymphocyte predominant type of Hodgkin's disease) show m-RNA for one light chain in the cytoplasm which can be visualized by in situ-hybridization. A new technique called "molecular histology" is applied to Hodgkin's disease. This is a single cell PCR of immunostained cells extracted from tissue sections by a micromanipulator. This technique enables us for the first time to demonstrate light chain and heavy chain gene rearrangements in Hodgkin cells of nodular sclerosis and mixed cellularity type. Hodgkin's disease seems to be no single entity but a heterogenous group of B- and possibly T-cell lymphomas. In the B-cell types Hodgkin cells are probably pre-B and B-cells.

Heterotopic small bowel transplantation was performed in allogeneic rats with and without cyclosporine. Syngeneic animals served as controls. Small bowel allografts, lymphoid tissues and small bowel of the host were investigated by immunohistochemistry using antibodies against T-cells and macrophages. During rejection, increasing numbers of macrophages infiltrated preferentially the deep layers of the small bowel wall, whereas only a slight T-cell infiltration was observed. No histological changes were noted in the organs of the host. Cyclosporine prevented lymphoid as well as macrophage infiltration of the transplant. Rejection monitoring of small bowel transplants is possible by investigation of macrophage infiltration in deep biopsies including the submucosa.

7 cases of familial hemophagocytic lymphohistiocytosis were investigated by morphology and immunohistochemistry. Typical infiltrates composed of macrophages and lymphoid cells were found in various locations such as lymph nodes, spleen, liver, brain, and skin. The macrophages were positive for typical macrophage antibodies (Ki-M1, Ki-M1P) and showed features of activation by displaying a strong reaction with antibodies against lysosomal antigens (Ki-M1P, Ki-M6, Ki-M7, Ki-M8). In addition, they showed antigenic similarity to antigen-presenting cells (Vit-6 pos., S 100 pos.) and no conclusive evidence of in situ proliferation (Ki-67 neg). The lymphoid cells were mainly composed of more or less proliferating T-cells and a few B-cells.

The problems of surgical technique, graft physiology and immunological reactions in small-bowel transplantation have been investigated in extended animal experiments. In these experiments, the fundamentals of a successful clinical application of small-bowel transplantation could be laid. A successful human small-bowel transplantation could be carried out by the Kiel Group for the first time in 1988. A graft which had been removed from a related donor showed a complete adaptation after 22 months, so that the patient became completely independent from parenteral nutrition. After that, in several cases small-bowel and combined liver and small-bowel transplantation have been carried out. Thus, the clinical small-bowel transplantation represents the causal therapy of short-bowel syndrome and should be developed in further clinical trials.

Plasmacytoid, T cells (PTC) occurring in cases of chronic non-specific lymphadenitis were investigated using a panel of monoclonal antibodies and cryostat sections. From the typical T cell antigens only CD4 was detectable on PTC. Antibodies directed against myelo-monocytic antigens such as Ki-M2, Ki-M6 (CD68), and Ki-M7 revealed positive reaction with these cells. The recently established monoclonal antibody Ki-M1P reactive with monocyte/macrophages shows a surface and granular cytoplasmic reactivity with PTC. This observation may indicate the myelo-monocytic origin. Ki-M1P detects a formalin resistant antigen and is thus applicable to conventionally processed paraffin sections as demonstrated in twenty cases of hystiocytic necrotizing lymphadenitis (KIKUCHI).

The semisynthetic third generation cephalosporin cefmenoxime was injected through the pars plana into the mid-vitreous in seven rabbit eyes. The drug dosage varied between 0.5 and 15 mg. Seven control eyes were injected only with 0.9% NaCl-solution. Electroretinography was performed before injection and 1 week post injection. The rabbits were anesthetized by intramuscular application of ketanine (Ketanest). Immediately after the second ERG the eyes were enucleated and prepared for both light and electron microscopy. Light microscopy showed only slight retinotoxic effects. Electron microscopy revealed beginning toxic necrosis of the outer segments of the photoreceptors following drug doses equal to or greater than 2 mg. Significant changes in the ERG were not noted in any of the treated eyes. The toxicity of cefmenoxime and other cephalosporins reported in the literature is discussed together with the clinical relevance of the findings.