An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.

Imaging of carcinoid tumors with iodine-123 metaiodobenzylguanidine.

Scintigraphy with 123I-radiolabeled metaiodobenzylguanidine (MIBG) was performed successfully in two patients with metastatic carcinoid tumor. The scintigraphic findings show diversity of the tumor deposits in the uptake of [123I]MIBG in the same patient and between patients.

Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison.

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.

Exogenous pigment in Peyer's patches.

Dark brown granular pigment was found consistently in macrophages in the deep aspect of adult Peyer's patches. Tissue sections from intestinal resections of 35 patients with a variety of pathologic diagnoses and of seven postmortem cases with no evidence of gastrointestinal disease were examined for the presence of this pigment. It was found in all patients over the age of 6 years (34 cases) but was not found in any children below that age (eight cases). Scanning electron microscopy with secondary and backscattered electron imaging and x-ray energy spectroscopy were performed on routine histologic sections. The pigmented macrophages contained aluminum and silicon, diffusely present throughout the cytoplasm, and numerous discrete foci of titanium. Pigment containing these same elements has also been found around dilated submucosal lymphatics, in mesenteric lymph nodes, and in some transmural inflammatory aggregates of Crohn's disease. The pigment probably is derived from the diet and actively taken up by Peyer's patches, which are able to incorporate inert particulate matter.

Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis?

In an immunohistochemical pilot study of 195 primary breast cancer patients with a 10-year median follow-up we found that patients with carcinomas who express p53 protein in the majority of their tumor cells (19% of the cases) have a considerably worse prognosis than those who do not. The effect of the presence of the protein is seen on disease-free interval (chi-square, 11.69; P < .001), overall survival (chi-square, 19.68; P < .001), and survival after relapse (chi-square, 4.93; P < .02), and is seen in node-negative (chi-square, 6.99; P < .009) and node-positive (chi-square, 13.05; P < .001) patients. Furthermore, the effect is most apparent in patients with infiltrating lobular and grade II infiltrating ductal carcinomas (chi-square, 27.97; P < .001) that have a rather heterogeneous clinical behaviour and are difficult to subdivide on the basis of currently available markers. Cox multivariate analysis shows that p53 majority staining is second only to node status in significance of effect on overall survival.

Eosinophilic infiltrates of the gastrointestinal tract.

There are two lesions which are often confused despite their quite distinct clinical and pathological differences: the inflammatory fibroid polyp and eosinophilic gastroenteritis. Other eosinophilic lesions likely to be encountered in the gut also pose problems of differential diagnosis.

Fat necrosis presenting as obscure abdominal mass: birefringent saponified fatty acid crystalloids as a clue to diagnosis.

AIMS: To describe the birefringent saponified fatty acid crystalloids seen in pancreatic fat necrosis. METHODS: A histological review, including polarising microscopy, of three cases of subacute or subclinical acute pancreatitis was performed. Histochemical analysis using Nile blue sulphate for lipid, Holczinger's copper rubeanate for fatty acids, and Alizarin Red S for calcium was performed in one case. Scanning electron microscopy and x-ray energy dispersive spectroscopic micro-analysis were performed in two cases. Necropsy pancreatic tissue, surgical archival tissue from cases of pancreatitis, and pancreatic and adipose tissue permitted to autolyse together in the laboratory, were also examined. The autolysed tissue was also examined histochemically. Stained and unstained sections were mounted in DPX and Canada balsam. Surgical material showing traumatic fat necrosis was reviewed. RESULTS: In each of the three cases there were subtle clues to subclinical pancreatitis. In neither surgical case was the true nature of the mass apparent to the operator. Histological analysis in all cases showed ghost adipocytes containing numerous polarising crystalloids, as well as some basophilic debris. Microanalysis showed calcium but no other substantial heavy element signals. Histochemical analysis showed a labile, polar, acidic lipid and the crystalloids behaved as calcium salts of free fatty acid. The crystalloids were not seen in archival material mounted in Canada balsam. No crystalloids were seen in traumatic fat necrosis. CONCLUSIONS: Little recognised, strongly birefringent, saponified free fatty acid crystalloids occurring in pancreatic fat necrosis may survive routine processing, and can point to the origin of obscure mesenteric masses related to subclinical pancreatitis.

Immunohistochemistry in district general hospitals in England and Wales.

The findings of a survey on the use of immunohistochemistry in district general hospitals in England and Wales are reported. Immunohistochemistry is used in most district hospitals, contributes to the accuracy and objectivity of some histopathological diagnoses, and is considered to be generally useful though not without drawbacks. Its expansion is being hindered by lack of funds for reagents and staff. In a few regions attempts are being made to rationalise expenditure and coordinate development of the service. We believe that if this can be done at a regional or national level then the relatively small cost entailed will be justified by a resulting improvement in the quality of patient care.

Granular cells as a marker of early amiodarone hepatotoxicity: a pathological and analytical study.

Two contrasting cases of amiodarone hepatotoxicity are described. In one, perivenular collections of swollen cells, probably macrophages, with granular cytoplasm in an otherwise nearly normal liver were observed. Transmission electron microscopy showed that the cytoplasmic granularity was due to lysosomal bodies of various sizes. X-ray energy and wavelength spectroscopic analysis showed a high iodine content in these lysosomal bodies, good presumptive evidence of the presence of amiodarone or one of its metabolites. In the second case there was a micronodular cirrhosis, and similar granular cells also containing iodine were seen in the fibrous connective tissue. These cases seem to represent the very early and late stages of amiodarone hepatotoxicity. In a patient taking this drug aggregates of swollen granular cells may be a sensitive and histopathologically useful marker of early amiodarone toxicity.

Coconut matting bezoar identified by a combined analytical approach.

A rare type of bezoar composed of coconut matting was found in the stomach of a caucasian man. The exact identity of the fibres was established by scanning electron microscopy, x-ray energy spectroscopy, and microscopic infrared spectroscopy. This report illustrates the importance of these techniques for identifying the nature of foreign material.

Silver deposition in the cervix after application of silver nitrate as a cauterising agent.

Large amounts of metallic silver pigment were found in 10 cervical biopsy specimens taken for the histological grading of cervical intraepithelial neoplasia (CIN). The assessment of CIN was made much harder because the pigment obscured the morphological detail of the epithelial cells, and in some it was very difficult to determine whether koilocytosis or CIN I was present. The silver can easily be removed by a simple chemical method.

Histopathological and microanalytical study of zirconium dioxide and barium sulphate in bone cement.

AIMS: To report the appearances of zirconium dioxide and barium sulphate in interface membranes, synovium, and other tissues around joint prostheses. METHODS: Histological sections from 23 specimens were reviewed by light microscopy and polarisation. Scanning electron microscopy and x ray microanalysis were performed on routinely processed paraffin wax sections. RESULTS: Polyethylene, metals, and polymethylmethacrylate cement debris were easily recognisable. Almost all the cement remnants contained either zirconium dioxide or barium sulphate, confirmed by microanalysis. The contrast media had characteristic light microscopic appearances. Zirconium was identified in macrophages away from cement remnants. CONCLUSION: The presence of radiographic contrast media in tissues around prosthetic joints is common but not widely recognised.

Proliferating cell nuclear antigen (PCNA) and nucleolar organiser regions in Hodgkin's disease: correlation with morphology.

AIM: To define the distribution of proliferating cell nuclear antigen (PCNA) and silver staining nucleolar organiser regions (AgNORs) in Hodgkin's disease. METHODS: PCNA was shown in a series of 34 cases of Hodgkin's disease using immunohistochemical methods. In a second series of 46 cases the AgNOR technique for interphase nucleolar organiser regions was studied. Both series comprised routinely fixed and processed paraffin wax sections of three main Rye subtypes. RESULTS: In all cases, regardless of Rye subtype, most Sternberg-Reed cells and mononuclear Hodgkin cells showed nuclear PCNA immunoreactivity and such cells had 15 or more AgNOR sites. The Hodgkin cells had, in general, about half the number of AgNORs seen in Sternberg-Reed variants. CONCLUSIONS: These data support the notion that Hodgkin's disease can be regarded as a high grade lymphoma, the large Hodgkin's and Sternberg-Reed cells being the (PCNA positive and AgNOR rich) neoplastic elements with high proliferative capacity. A smaller proportion of the associated cells also showed evidence of proliferation.

Combined light and electron microscope in routine histopathology.

We report our experience with a prototype combined light and electron microscope (the LEM 2000) with particular reference to its application to routine surgical histopathology. We found its major advantages over conventional transmission electron microscopies were due to the large grid size (7 mm diameter), low magnification capacity (x 250), and the built-in microprocessor for recording areas of interest. These features combine to reduce sampling errors and greatly facilitate orientation and relocation of fields of diagnostic importance.

Clinicopathological spectrum of late postpartum renal failure; two contrasting cases.

The clinical and renal biopsy findings from two patients in whom renal functional abnormalities developed in the late postpartum period are described. Both biopsies showed fibrin deposition in the renal vasculature, in one case marked and in the other mild. The patient with the more severely damaged kidney subsequently died, and the other is alive but with evidence of slowly progressing renal damage. The clinicopathological spectrum and pathogenesis of late postpartum renal failure are discussed.

Varied light and scanning electron microscopic appearances of barium sulphate in smears and histological sections.

The various light and scanning electron microscopic appearances of barium sulphate in smears and in histopathological lesions in sections are illustrated. One type of barium sulphate (E-Z-HD) includes much larger, bright birefringent particles and has very different appearances from other widely used types. Such larger particles in sections were not originally suspected to be barium sulphate and were identified only by energy dispersive x ray analysis in a scanning electron microscope. This form of barium sulphate is used for double contrast upper gastrointestinal radiography, and is not thought to have been responsible for the lesions in which it has been observed by us.

Prognostic value of proliferating cell nuclear antigen in gastric carcinoma.

A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising.

Parathyroid carcinoma associated with chronic renal failure and previous radiotherapy to the neck.

Carcinoma of the larynx was treated by irradiation followed by laryngectomy in a man who had been receiving regular haemodialysis for two years. At least one, and probably two, parathyroid glands were removed at this time, and the remaining two were removed three years later for tertiary hyperparathyroidism. A portion of one gland was implanted into the forearm. The forearm implant was resected the following year for recurrent hypercalcaemia. Six years later, again with recurrent hypercalcaemia, he died of bronchopneumonia. Metastatic parathyroid carcinoma was found in the apex of the left lung. The source of this parathyroid tissue and the possible role of irradiation in the pathogenesis of parathyroid cancer in this patient were investigated.

Primary Gut Lymphomas.

Differences in behaviour and morphology between primary gut lymphomas and primary nodal lymphomas have recently become increasingly apparent. In this article we review the principal clinicopathological types of primary gut lymphomas and suggest an approach to their classification which is in accord with our own experience and, we believe, the recent literature on the subject.

123I metaiodobenzylguanidine (MIBG) scintigraphy of retinoblastoma: preliminary experience.

123I metaiodobenzylguanidine (MIBG) is a radiopharmaceutical used for imaging neural crest tumours. The possibility of using 123I MIBG for imaging retinoblastomas has been assessed in this pilot study. Ten patients were studied, nine with clinically and histologically proved retinoblastomas and one with Coats's disease. 123I MIBG scintigraphy correctly identified the neoplasm in eight patients but gave a negative result in two, one of whom had Coats's disease and the other a retinoblastoma which proved to be extensively necrotic on histological examination. These preliminary results suggest that 123I MIBG scintigraphy may have a role in differentiating retinoblastomas from lesions that simulate them.