Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast

Breast carcinomas, either positive or negative with the Grimelius' silver procedure, benign fibroadenomas, duct papillomas, and areas of histologically normal breast tissue were tested immunocytochemically with the mouse monoclonal antibody LK2H10 directed against human chromogranin. This is regarded as a general stain for polypeptide-hormone-producing cells and tumors. In 3 of the 9 cases of argyrophilic carcinoma, but in none of 12 ductal infiltrating carcinomas, chromogranin-positive cells were found: the number of reactive cells was very low in 1 case, while in the other 2 carcinomas about 50% of the argyrophilic cells appeared stained. In areas of histologically normal breast tissue, rare argyrophilic chromogranin-positive cells were detected. This study is the first reported evidence concerning the presence of endocrinelike cells probably belonging to the diffuse neuroendocrine system in the normal mammary parenchyma. Our data are consistent with the endocrine nature of at least some of the breast argyrophilic carcinomas.     

Ultrastructure and chromogranin A immunogold labelling of ECL cell carcinoids

Poorly differentiated neuroendocrine cells can be difficult to recognise. Sensitive methods are needed to label cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, enterochromaffin-like cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human enterochromaffin-like cell carcinoids. Electron-dense granules of poorly differentiated cells were less intensely labelled than granules in well-differentiated cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 degrees C compared to a microwave at 100 degrees C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.     

The relationship between feathering abnormalities ("nakanuke") and tumour production in chickens inoculated with reticuloendotheliosis virus

High concentrations of T strain reticuloendotheliosis virus (REV), which had been maintained by passage in 1-day-old chicks, produced reticuloendotheliosis tumours and deaths 8 to 13 days after inoculation. At lower concentrations fo virus inoculum, deaths did not occur but feathering abnormalities ("nakanuke") was regularly produced. These results indicate that the oncogenic T strain of REV may also produce abnormal feathering. The oncogenic potential was decreased when REV-T strain maintained in 1-day-old chicks was passaged once in duck embryo fibroblast (DEF) cultures. After three passages in DEF cultures the same virus strain had lost oncogenicity but retained the ability to induce abnormal feathering. REV-T strains which had been maintained over long periods in chicken embryo fibroblast (CEF) cell culture also lacked oncogenic potential but produced abnormal feathering in chickens. Tumours were not produced during a 2-month observation period by either REV-T which had been passaged three times in DEF culture or by the Japanese KI strain of REV which is not known to be oncogenic, but abnormal feathering was induced in both groups of inoculated chickens. Serological differences were not detectable with the indirect fluorescent antibody test among strains of REV with and without oncogenic potential.     

Gastric carcinoids of ECL cells. Pathological and clinical analysis of eight cases

Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non-antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) "simple hyperplasia", b) "nodular hyperplasia", and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non-antral portion of the stomach with possible therapeutical implications.     

Plasma cell tumour progression in iMycEmu gene-insertion mice

The authors have recently reported that gene-targeted iMyc(Emu) mice that carry a His(6)-tagged mouse Myc cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, Emu, are prone to 'spontaneous' neoplasms of the B-lymphocyte lineage. The present study has used histological, immunohistochemical, and molecular genetic methods to investigate a subset of these neoplasms referred to as extraosseous plasmacytomas (PCTs). It is shown that 20.8% (20/96) of tumour-bearing iMyc(Emu) mice on a mixed genetic background of segregating C57BL/6 and 129/SvJ alleles develop PCT by 500 days. The Myc(His)-induced PCTs produced monoclonal immunoglobulin and developed in the gut-associated lymphoid tissue (GALT), particularly the mesenteric node and Peyer's patches. The PCTs overexpressed Myc(His), at the expense of normal Myc, and exhibited gene expression changes on cDNA macroarrays that were consistent with Myc(His)-driven neoplasia. Surprisingly, in one of three PCT-derived cell lines, Myc(His) was 'replaced' by a naturally occurring T(12;15) translocation, which changed the mode of Myc deregulation from gene insertion (Myc(His) transgene) to chromosomal translocation (juxtaposition of normal Myc to the immunoglobulin heavy-chain locus Igh). These findings provide evidence that recreation of the mouse PCT-associated T(12;15)(Igh(Emu)-Myc) translocation by gene insertion in mice results in the predictable development of PCTs in approximately one-fifth of the tumour-bearing mice. Myc(His)-driven PCTs recapitulate aspects of human plasma cell neoplasms, for which relatively few models exist in mice. For example, PCT development in the iMyc(Emu) mice may provide a good system to study the mechanism by which human MYC facilitates the progression of plasma cell myeloma (multiple myeloma) in humans.     

Studies on spondylolisthesis ("kinky back") in broiler chickens

Spondylolisthesis was diagnosed in paralyzed commercial broiler chickens using radiology. Six affected birds when held in a favourable environment recovered sufficiently to be used for breeding. Spinal deformation was still present in these birds when they were necropsied at one year of age. One hundred and sixty pedigreed chicks produced from these birds were raised intermingled with 151 commercial broilers. Six of the experimental chicks were clinically affected with spondylolisthesis while none of the control chicks were affected. In continued studies the experimental chicks were inbred and the control chicks randomly bred for a further two generations. In the second generation 13% of the experimental chicks were clinically affected with spondylolisthesis while in the third generation 9% were affected. Less than half a per cent of the control chicks from both second and third generations were affected. No consistent relationship between incidence of spondylolisthesis, hatch, brooding environment or ration was noted. A higher incidence of scoliosis was encountered in the experimental birds than in the control birds. No relationship between deformed legs and spondylolisthesis was apparent. The incidence of leg deformities was higher in the control than in the experimental birds.     

Recurrence risk in the Angelman ("happy puppet") syndrome

We report on two sibs with Angelman "happy puppet" syndrome. Out of 48 families reported in the literature, this is only the fourth family with affected sibs. A review of the literature shows a low but not negligible recurrence risk. Different explanations for this are discussed.     

Urgent ("stat") testing in chemical pathology--position paper.

Increasingly heavy use is made of the pathology laboratory in many hospitals. This can cause problems, particularly with regard to urgent ("stat") tests, where a result is required in a short time. Many small laboratories are forced to offer a wide battery of tests, many of which may not help greatly in the acute diagnosis and/or management of the patient, and are expensive and inconvenient to perform. This paper addresses the questions as to which (chemical pathology) analytes should be available as emergency ("stat") tests, and how long should it take for results to come back.     

Prospective memory impairment in abstinent MDMA ("Ecstasy") users

Introduction: Quantitative evidence has begun to emerge where human studies suggest that repeated recreational use of +/- 3,4-methylenedioxy-methamphetamine (MDMA or "Ecstasy") produces lasting impairments in explicit memory. The purpose of this investigation was to further explore the nature and pattern of component memory processes in abstinent MDMA users. Methods: Accordingly, 15 MDMA users and 17 matched normal controls completed a brief neuropsychological test battery composed mainly of the Rivermead Behavioural Memory Test (RBMT), a Stem-Completion task, and the Vocabulary subtest of the Wechsler Adult Intelligence Scale-III (WAIS-III). Results: MDMA users were found impaired in terms of episodic prospective memory, as medium to large effects were observed between groups on time-based Appointment and event-based Message subtests of the RBMT. The results of this study also indicate that the ability to recall a future appointment may be related to the frequency of MDMA use and the absolute number of times MDMA was used. Conclusion: Further research is warranted into the underlying neurological manifestations of such deficits, such as investigating the relation between the neurotransmitter serotonin and the component processes of memory.     

Acute respiratory insufficiency syndrome ("shock lung") in adults]

The causes of the development of acute respiratory insufficiency ("shock lung") may include any shock, burn disease, posttransfusion syndrome, hyperoxygenation and trauma of the lungs. Morphologically, against the background of inflation of the lung parenchyma, bilateral fine-focus atelectases, focal disorders of the circulation of the type of leukostases, sludge, leading to extensive hyalin (spodogenic) thromboses, develop. Secondarily, a small-focus edema, hemorrhages, sometimes, hyalin membranes, develop. Atelectases are initially reversible, but later, when surfactant desintegrates against the background of circulatory disorders, they become stable. The main mechanism of the development of this process consists in the release, during shock, of biologically active amines in the lungs leading to circulatory disorders in them. This is attested to by the possibility of producing the "shock lung" picture in intact animals by inoculation into their blood of plasma from the animals in a shock condition.     

Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell ("sugar") tumor versus malignant melanoma

A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.     

Trichoblastic carcinoma ("malignant trichoblastoma") with lymphatic and hematogenous metastases.

We report an aggressively behaving malignant trichogenic tumor arising in a trichoblastoma (TB) with widespread lymphatic and hematogenous metastases in a 55-year-old man with a concomitant B-cell chronic lymphocytic leukemia. The primary tumor had been present and unchanged for as long as 40 years before excision. Typical trichogenic TB with dystrophic calcification and even ossification was still present peripheral to the malignant transformation. The malignant neoplasm consisted of basaloid cells, spindle cells arranged in fascicles and densely packed rounded nests or "cell balls." The metastases consisted of immature basaloid cells and cell balls, and the recurrences became successively more undifferentiated. The residual TB reacted with antibodies to cytokeratin (CK) 6, 8, 14, and 17 and focally to S-100; the malignant primary tumor reacted uniformly with antibodies to vimentin and only focally with antibodies to CK and S-100. The metastatic tumor had lost epidermal CK expression but maintained expression of S-100 in paraffin-embedded tissues. Trichoblastic differentiation was confirmed in frozen tissues with antibodies to hair keratins. No expression of p53 or bcl-2 was identified, but p-glycoprotein (MDR-1 gene related) was expressed by primary and metastatic tumor cells. We believe that this neoplasm is best classified as a trichoblastic carcinoma arising in a TB in association with a B-cell chronic lymphocytic leukemia. This case illustrates that TBs have the potential for malignant transformation and aggressive behavior.     

Genetics of acheiropodia ("the handless and footless families of Brazil")

The acheiropodia data are shown to be consistent with the hypothesis of a fully penetrant gene in the homozygous state. The expressivity is shown to be generally constant, with some minor variation between individuals as well as between the two sides of the same affected person.