[Classification of neoplastic disorders of the haematopoietic system]. / Klassifikation von Neoplasien des hämatopoietischen Systems.

The present article is written in an attempt to illustrate the ongoing diagnostic progress by presenting some examples of pre-existing and newly defined entities. The World Health Organisation proposed in 2001 a "Classification of Tumours of the Haematopoietic and Lymphoid Tissues". Relying on the broadest consensus possible, it received high acclamation by both clinicians and pathologists. The approach is based on cell lineage assignment including morphology and immunophenotype, but also relies on cytogenetic and clinical features in order to define disease entities to an extent as far as possible. The diagnostic criteria for myeloid, lymphoid and histiocytic neoplasms have been compiled by an international group of 51 experts assembled in ten disease-related committees. In order to cover the interests of daily haematological practice, selected topics are focussed including chronic and acute myeloid neoplasias, precursor lymphoid neoplasias, mature B-, T- and NK-cell lymphomas, Hodgkin lymphoma as well as histiocytic and dendritic cell neoplasias.

Posttransplant CD30+ anaplastic large cell lymphoma with skin and lymph node involvement.

Posttransplant (i.e. status with the transplant present) lymphoproliferative disorders (PTLD) are common conditions in transplant recipients. Most examples are of B cell origin, and CD30+ T cell PTLD are very rare. We report a CD30+ anaplastic large cell lymphoma (ALCL) in the skin of the right lower leg and in draining lymph nodes of the right inguinal region in an immunosuppressed 59-year-old male who had received a renal graft 9 years previously. Unlike the vast majority of PTLD, an incomplete T cell immunophenotype was observed, and there was evidence of T cell lineage at the genetic level reflected by a rearranged T cell receptor gamma gene. The neoplastic cells were non-reactive to the anaplastic lymphoma kinase (ALK) 1 protein. In addition, Epstein-Barr virus and human herpesvirus 8 sequences were absent. Arguments against a primary cutaneous ALCL, which is also ALK-1 negative, include systemic presentation at the time of initial diagnosis and immunoreactivity of the neoplastic cells to epithelial membrane antigen. Typically, our rare example of a posttransplantation systemic ALCL showed an aggressive behaviour and a poor response to both chemotherapy and local irradiation.

Control of autofluorescence of archival formaldehyde-fixed, paraffin-embedded tissue in confocal laser scanning microscopy (CLSM).

Confocal laser scanning microscopy (CLSM) offers the advantage of quasi-theoretical resolution due to absence of interference with out-of-focus light. Prerequisites include minimal tissue autofluorescence, either intrinsic or induced by fixation and tissue processing, and minimal background fluorescence due to nonspecific binding of the fluorescent label. To eliminate or reduce autofluorescence, three different reagents, ammonia-ethanol, sodium borohydride, and Sudan Black B were tested on paraffin sections of archival formaldehyde-fixed tissue. Paraffin sections of biopsy specimens of human bone marrow, myocardium, and of bovine cartilage were compared by CLSM at 488-nm, 568-nm and 647-nm wavelengths with bone marrow frozen sections fixed either with formaldehyde or with glutaraldehyde. Autofluorescence of untreated sections related to both the specific type of tissue and to the tissue processing technique, including fixation. The reagents' effects also depended on the type of tissue and technique of tissue processing, including fixation, and so did the efficiency of the reagents tested. Therefore, no general recipe for the control of autofluorescence could be delineated. Ammonia-ethanol proved most efficient in archival bone marrow sections. Sudan Black B performed best on myocardium, and the combination of all three reagents proved most efficient on paraffin sections of cartilage and on frozen sections fixed in formaldehyde or glutaraldehyde. Sodium borohydride was required for the reduction of unwanted fluorescence in glutaraldehyde-fixed tissue. In formaldehyde-fixed tissue, however, sodium borohydride induced brilliant autofluorescence in erythrocytes that otherwise remained inconspicuous. Ammonia-ethanol is believed to reduce autofluorescence by improving the extraction of fluorescent molecules and by inactivating pH-sensitive fluorochromes. The efficiency of borohydride is related to its capacity of reducing aldehyde and keto-groups, thus changing the fluorescence of tissue constituents and especially of glutaraldehyde-derived condensates. Sudan Black B is suggested to mask fluorescent tissue components.

Late-onset eccrine angiomatous hamartoma: clinical, histological and imaging findings.

Eccrine angiomatous hamartoma (EAH) is an exceedingly rare benign tumor-like lesion prevalent in childhood which may produce pain and marked sweating. Although an aggressive treatment is not generally indicated, surgery may be considered in severe cases. In this report we present novel morphological findings by immunophenotyping, document the first MRI findings in EAH and emphasize the importance of preoperative imaging of such lesions.

Acute asymmetric upper nasal quandrantanopsia caused by a chiasmal colloid cyst in a patient with multiple sclerosis and bilateral retrobulbar neuritis.

PURPOSE: To report a patient with multiple sclerosis and a history of sequential bilateral retrobulbar neuritis, who developed new onset of highly asymmetric upper quadrantanopsia. DESIGN: Interventional case report. METHOD: A 36-year-old woman with multiple sclerosis and bilateral retrobulbar neuritis developed an acute asymmetric upper nasal quadrantanopsia. RESULTS: Magnetic resonance imaging of the brain revealed a cyst that caused chiasmal compression and bilateral visual field defects. CONCLUSION: New onset of bilateral visual field defects in a patient with diagnosed multiple sclerosis is likely to be caused by a new attack of the demyelinating disease. In this case, a newly diagnosed chiasmal colloid cyst was the cause of visual field defects.

Monoclonal antibody SM047 as an immunohistochemical marker of ovarian adenocarcinoma.

AIMS: This study describes the generation of a monoclonal antibody designated SM047 which binds to an epitope that is displayed by a multivalent antigen associated with the glycocalyx of ovarian adenocarcinoma cells. The study also investigates SM047 staining in adenocarcinomas of diverse sites in order to determine whether the antibody is specific for ovarian adenocarcinoma and of value in the confirmation of an ovarian origin when the site of primary tumour is unknown. METHODS AND RESULTS: SM047, an IgM monoclonal antibody, was the product of hybridoma cells derived from fusion of SP2 myeloma cells with splenocytes of a mouse that had been immunized with a membrane preparation of tumour (ovarian serous cystadenocarcinoma) and boosted with cells from a cell line established from a similar tumour in a different patient. Sixty-two primary ovarian adenocarcinomas (28 serous, 23 mucinous, five endometrioid and six clear cell), 69 adenocarcinomas arising primary at other sites and 10 mesotheliomas were stained with SM047. There was positive membrane staining, which was usually strong and widespread, in 27 of 28 ovarian serous carcinomas and in all ovarian endometrioid and clear cell carcinomas. Most ovarian mucinous tumours were negative or exhibited weak cytoplasmic staining. Staining was variable in the other tumours but there was positive staining of most endometrial, endocervical and pancreatic adenocarcinomas. Most colonic adenocarcinomas were negative or exhibited weak cytoplasmic staining. CONCLUSIONS: SM047 is strongly expressed in most ovarian serous adenocarcinomas and in other female genital tract adenocarcinomas, with the exception of ovarian mucinous tumours. The antibody may be useful in confirming the ovarian origin of an adenocarcinoma when used as part of a larger panel. This is especially so in the distinction between a non-mucinous ovarian adenocarcinoma, which usually exhibits strong membranous staining, and a colonic adenocarcinoma which is usually negative or exhibits weak cytoplasmic staining. These findings need to be confirmed by further study of larger numbers of cases.

Lipomatous meningioma: a clinicopathologic study of 18 cases with special reference to the issue of metaplasia.

We report 18 cases of lipomatous meningioma occurring in patients aged 14 to 79, most being females (72%). Sixteen were supratentorial and 2 involved the spinal meninges. Follow-up ranged from 1 to 120 months. Fifteen patients were cured with surgery alone and 3 (17%) experienced a recurrence at 7, 8 and 24 months. Of these, one died with disease 4 years after resection of the primary lesion. Histologically, 12 tumors were meningothelial, 3 transitional, 2 showed myxoid stromal changes and 1 was microcystic. The 2 spinal tumors were atypical. The proportion of fatty cells ranged from 10 to 90%. These resembled mature adipocytes or less commonly lipoblasts. Xanthomatous meningothelial cells were also noted in 6 tumors (30%). Both conventional meningothelial as well as lipid-laden cells exhibited epithelial membrane antigen immunoreactivity. In addition, occasional cells resembling mature adipocytes showed reactivity for S-100 protein. Ultrastructurally, lipidization of neoplastic cells varied from intracytoplasmic lipid droplets to a single massive globule. Moreover, lipid-laden meningothelial cells featured interdigitating cell membranes and well-formed desmosomes. Lipid droplets were not membrane-bound. In that metaplasia denotes differentiation of one mature cell type to another, lipid accumulation in meningiomas cannot be considered true metaplasia since their lipid-laden cells retain the immunophenotype and ultrastructural features of meningothelium. We suggest that this distinctive subset of meningiomas be termed "lipidized meningiomas" rather than being included in the metaplastic category.

[Multiple pigmented basalioma of the scalp in a patient with Curschmann-Steinert myotonia dystrophica. Confirmation of a rare symptom constellation]. / Multiple pigmentierte Basaliome im Capillitium bei Myotonia dystrophia Curschmann-Steinert. Bestätigung einer seltenen Symptomenkonstellation.

A 50-year-old woman presented with myotonic dystrophy (Curschmann-Steinert disease) and multiple pigmented basal cell carcinomas of the scalp. She also had typical androgenetic alopecia seen in this disorder. In 1986 Stieler and Plewig described the first patient with myotonic dystrophy and multiple basal cell carcinomas. There may be a genetic predisposition for cutaneous tumors with follicular origin, as multiple pilomatricomas also occur frequently in such patients.

Malakoplakia of the colon in an infant with severe combined immunodeficiency (SCID) and charge association.

We report on malakoplakia of the colon observed in a six month old girl in a setting of severe combined immunodeficiency (SCID) and a malformational syndrome termed CHARGE association. By the age of six months, hemorrhagic diarrhea had developed, and multiple ulcers were seen at colonoscopy. The biopsy specimen showed ulcerating malakoplakia. Immunodeficiency was primarily reflected by deprivation of CD4 cells in the peripheral blood, and CT scans failed to detect structures consistent with a normal thymus. There were also polylymphadenopathy and chronic erythroderma. The lymph node showed extreme hypoplasia of the follicular cortex and marked expansion of the paracortex. B cell counts progressively declined, and plasma cells were absent both in intact mucosa of the colon and in a lymph node. The patient died at eighteen months of respiratory failure following recurrent airway infections. Pediatric malakoplakia of the colon, though rare, may be regarded as an example of opportunistic bacterial infection in an immunocompromised host. Combined immunodeficiency (CID) has to be considered in such instances, in particular when malformational syndromes coexist affecting the development of the thymus.

Anti-neuronal nuclear autoantibodies, types 1 and 2: their utility in the study of tumors of the nervous system.

This is a comprehensive immunohistochemical study of selected archival tumors of the nervous system applying human anti-neuronal nuclear autoantibodies of types 1 and 2 (ANNA-1 and -2), serum markers of paraneoplastic syndromes associated primarily with small cell lung cancer (SCLC). Neither ANNA-1 nor ANNA-2 bound to glial tumors regardless of histological grade and subtype; instead they labeled neurons in overrun normal parenchyma. Central neurocytomas and the neuronal components of mixed glioneuronal tumors were also immunoreactive for both. In addition, varying proportions of tumor cells were stained in dysembryoplastic neuroepithelial tumor, subependymal giant cell astrocytoma (SEGA), tuber and neuroblastoma. All other tumors were nonreactive, namely choroid plexus papilloma, pituitary adenoma, pineocytoma, pheochromocytoma, thymic and pulmonary carcinoid, chordoma, meningioma, schwannoma and metastatic melanoma. SCLC was immunonegative for ANNA-1 and ANNA-2 in paraffin preparations, but displayed strong immunoreactivity for both in frozen sections: this discrepancy was not observed in other tumors studied. In conclusion, the human IgG autoantibodies ANNA-1 and ANNA-2 provide novel tools for studying the cytogenesis of tumors of the nervous system in that they permit the identification of both normal and neoplastic, poorly differentiated and small neuronal cells that may escape detection using commercially available anti-neuronal antibodies.

Amyloidomas of the nervous system: a monoclonal B-cell disorder with monotypic amyloid light chain lambda amyloid production.

BACKGROUND: Amyloidomas or localized tumor-like amyloid deposits rarely affect the nervous system. To the authors' knowledge, no comprehensive studies on central and peripheral nervous system amyloidomas have been published. The amyloid subtype of amyloidomas of the nervous system only recently was characterized and almost invariably was found to be of amyloid light chain (AL) lambda type. The nature of the plasma cell population responsible for AL amyloid production has not been investigated further. METHODS: The current analysis included the clinical findings, neuroimaging characteristics, and pathology of seven amyloidomas (four cerebral and three involving peripheral nerves). All were subjected to histochemical staining (Congo red, thioflavine S) and to immunohistochemical study using primary antibodies detecting serum amyloid component P, serum amyloid protein A (SAA), transthyretin, beta2 microglobulin (beta2m), and free immunoglobulin (Ig) light chain. For the detection of mRNA of light chain Ig, fluorescein-conjugated kappa and lambda mRNA oligonucleotide probes were used. For the assessment of B-cell clonality, polymerase chain reaction (PCR) was applied on extracted DNA from two cases using VH FRIII and JH primers. Two cases were assessed ultrastructurally. RESULTS: All amyloidomas were organ restricted and unrelated to systemic amyloidosis. The clinical symptoms of the cerebral lesions were nonspecific, whereas neurologic deficits were noted in the distribution of the involved peripheral nerves. Cerebral deposits, either solitary or multiple, were associated spatially with the choroid plexus and secondarily extended into white matter. All peripheral nerve amyloidomas involved the gasserian ganglion of the trigeminal nerve. Imaging by computed tomography and magnetic resonance imaging scans revealed hyperdense and contrast-enhancing mass lesions unassociated with significant edema. Immunohistochemically, the amyloid was present in the interstitium and within the walls of the intralesional vessels, was invariably of AL lambda subtype, and was negative for free Ig kappa light chains, SAA, transthyretin, and beta2m. Plasma cells along the perivascular sheaths and occasionally squeezed between amyloid masses showed no cytologic atypia. In situ hybridization for Ig light chain mRNA reflected a massive preponderance of lambda-producing cells. PCR revealed monoclonal rearrangement of the heavy chain Ig gene. CONCLUSIONS: The results of the current study provide strong support for the concept that amyloidomas of the nervous system are neoplasms of an AL lambda-producing B-cell clone capable of terminal differentiation. Nevertheless, all seven patients lacked clinical evidence of an aggressive or systemic lymphoplasmacytic neoplasm. Unlike plasmacytomas, the relatively indolent course of most nervous system amyloidomas is reminiscent of the similarly indolent biologic behavior of extranodal, low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

[Systemic fibrosis (generalized form of Ormond's disease). Report of a case which achieved complete remission with cyclophosphamide and corticosteroids]. / Systemische Fibrose (generalisierte Form des Morbus Ormond). Bericht über einen Fall, der mit Cyclophosphamid und Kortikosteroiden eine komplette Remission erlangte.

A 51-year-old engineer was admitted with progressive lower back pain which had started 4 months before. We found an elevated ESR and anemia. Chest X-ray showed bilateral polycyclic thickening of the pleura, and abdominal CT examination revealed a paraaortic tumorous lesion and a solid kidney tumor with a diameter of 5 cm on the left side. During the course of the disease we also observed an infiltration in the apex of the upper lobe of the left lung. Histological examination showed fibrotic tissue typical of Ormond's disease in the kidney tumor as well as in the pulmonary infiltrate. We diagnosed a systemic form of retroperitoneal fibrosis. Treatment with cyclophosphamide (combined with prednisone during the first 4 months) resulted in complete remission of the disease.

Protothecosis in an HIV-positive patient.

This is the first report of localized tendosynovial human protothecosis in an HIV-positive host. The lesion appeared as a nodule in the extensor face of the thumb. A simple excision was performed, and histology confirmed numerous granulomas, some with central fibrinoid necrosis. Enormous numbers of prototheca were found in periodic acid-Schiff and Gömöri methenamine silver strains, evidencing endosporulation with diagnostic morula- or daisy-like sporangia. The presence of prototheca species was confirmed by direct immunofluorescence with the specific conjugate. The cellular response estimated by the relative number of polymorphonuclear leukocytes, lymphocytes, and plasma cells was minimal, although granuloma formation was unaffected. The infective agents were found either extracellular or harbored by macrophages and giant cells.

Epulis: a clinicopathological study of 120 patients with emphasis on recurrent lesions.

A total of 138 surgical excision specimens from 120 patients presenting clinically with epulis was classified by histopathological criteria into giant cell-, granulomatous- and fibromatous-type lesions. Clinical data suggest that local irritants are an important pathogenetic factor. Histopathological analysis revealed that epulides represented self-limiting, reactive gingival overgrowths of granulation tissue displaying common morphologic features in all three histologic types. The transition of a given histologic type of epulis into another, as observed in recurrent lesions, is consistent with the concept of a common histogenetic entity.

[Oral non-Hodgkin lymphomas and Epstein-Barr virus]. / Orale non-Hodgkin lymphome und Epstein-Barr virus.

The oropharynx is the site of primary infection and further propagation of the Epstein-Barr virus (EBV). From here, virus is shed to saliva and infects peripheral blood lymphocytes. Eight oral Non-Hodgkin lymphomas (NHL) were investigated for the presence of EBV both by immunohistochemistry for the latent membrane protein (LMP) and a PCR-strategy for general and subtype-specific viral sequences. All but one NHL turned out to be negative both by LMP and PCR. EBV general sequences and of the two viral subtypes A and B were found in an HIV-1+ patient. It is concluded that it is not the localisation which predetermines NHLs to EBV-positivity but merely the underlying disease (this study) or the type of tumour (previous studies).