Chronic myelomonocytic leukemia revealed by uncontrollable hematuria.

Nephrectomy was performed for uncontrollable unilateral hematuria in an apparently healthy 72-year-old man. The suburothelial connective tissue of the kidney was infiltrated by primitive myeloid cells with associated acute vasculitis and foci of extramedullary hematopoiesis. Subsequently, the patient was shown to have chronic myelomonocytic leukemia. Although renal involvement and vasculitis have been recorded previously in chronic myelomonocytic leukemia, this is the first occasion, to our knowledge, where their concurrence resulted in such a spectacular presentation.

Real-time quantitative analysis of E-cadherin expression in ret/PTC-1-activated thyroid neoplasms.

Papillary thyroid carcinoma (PTC), the most common variety of thyroid cancer, is found in a variety of morphologic variants, usually grows slowly, and is clinically indolent, although rare, aggressive forms, with local invasion or distant metastases, occur. Our group has previously demonstrated an association between Hashimoto thyroiditis and ret/PTC-1 activation, and have hypothesised that c-ret activation might be implicated in immune reaction to thyroid epithelium. The objective of this study was to examine expression of the cellular adhesion molecule, E-cadherin, in various thyroid tumor types and Hashimoto thyroiditis in the context of ret/PTC-1 positivity by using laser capture microdissection and TaqMan reverse transcription-polymerase chain reaction (RT-PCR). Variable down-regulation of E-cadherin among carcinomas was demonstrated, with anaplastic carcinomas showing little or no expression. Follicular thyroid carcinomas consistently had significantly decreased E-cadherin expression compared with papillary thyroid carcinomas. The ret/PTC-1-positive papillary thyroid carcinoma (PTCret+) and Hashimoto thyroiditis cases had consistently lower E-cadherin expression levels than the corresponding ret/PTC-1-negative papillary carcinomas (PTCret-), suggesting not only an association between ret activation and the loss of cellular adhesion but also, more significantly, an association between papillary thyroid carcinoma and Hashimoto thyroiditis.

Assessment of ret/PTC-1 rearrangements in neoplastic thyroid tissue using TaqMan RT-PCR.

Among oncogenes studied in thyroid cancers, a specific activated form of c-ret has been found in a minority of papillary thyroid carcinomas (PTCs). In these tumours, c-ret is activated when by somatic rearrangements, the intracellular domain of RET is juxtaposed with the amino-terminal portion of a different donor gene such as H4, thereby generating a chimeric transcript (ret/PTC-1). The functional effects of c-ret activation and its prognostic implications are currently unclear. This study was undertaken to assess the frequency of RET/PTC-1 expression, any distinctive features of positive tumours to which it might be related, and its prognostic importance. Archival material from 88 thyroid neoplasms [50 PTCs, eight anaplastic carcinomas (ATCs), 25 follicular thyroid carcinomas (FTCs) and five follicular adenomas (FAs)] were analysed for ret/PTC-1 and H4 expression using 5' nuclease assay (TaqMan RT-PCR). RNA from the TPC-1 cell line was included as a positive control for c-ret activation. No FTC or FA displayed activation of ret/PTC-1, though all expressed H4. c-ret activation was found in 24% of PTCs (12 of 50), in 87.5% of ATCs (7 of 8), and in 33% of the combined PTC/ATC group. The frequency of c-ret activation in the aggressive ATC variants noted here suggests that ret/PTC-1-positive PTCs might also have a similar poor prognosis and a follow-up study on this cohort is in progress. Ninety per cent of ret/PTC-1-positive tumours failed to express H4, a phenomenon that has not been described previously and which may have considerable bearing on tumour morphology. A statistically significant proportion (58%) of ret/PTC-1-positive, H4-negative PTCs was associated with chronic inflammatory cell infiltration of the tumour and/or the surrounding thyroid. This association has not been reported previously.

ret/PTC-1 Activation in Hashimoto Thyroiditis.

Activation of ret/PTC-1 has been documented in a minority of papillary thyroid carcinomas (PTC). In a recent study, the authors' group detected the presence of ret/PTC-1 in association with a background of florid lymphocytic thyroiditis (LT) in 58% of cases of PTC studied, which prompted them to examine the incidence of RET/PTC-1 expression in 27 examples of various forms of nonlymphomatous lymphoid infiltration of the thyroid by using TaqMan RT-PCR. Overall, 21 cases (78%) were found to express the chimeric transcript of ret/PTC-1. Eighteen cases of Hashimoto thyroiditis were positive (95%), and, of these, three had concomitant PTC while the remainder had no histologic evidence of associated malignancy. Three cases of lymphocytic thyroiditis demonstrated activated ret/PTC-1 (43%), two having associated PTC. These data suggest either that ret/PTC-1 is an indicator of follicular thyroid cell activation or that ret/PTC-1 activation is an early event in malignant transformation. If the latter is the case, it may be that, in a defined subset of the cell population, ret/PTC-1 activation elicits an autoimmune response, which, while possibly curtailing the development of PTC in the majority of cases, results in destruction of the thyroid parenchyma. Int J Surg Pathol 8(3):185-189, 2000

TSH receptor status of thyroid neoplasms--TaqMan RT-PCR analysis of archival material.

Regulation of thyroid follicular cell proliferation and function is mediated by the interaction of TSH with its receptor (TSHr) on the plasma membrane. While it is recognized clinically that responsiveness of thyroid epithelial tumours to TSH varies with the histological type and grade of neoplasm, the level of TSHr expression in these different tumours has not been quantified hitherto. The aim of this study was to provide this information. Total RNA was extracted from 125 samples of formalin-fixed, paraffin-embedded thyroid tissue comprising 48 papillary (PTC), 29 follicular (FTC), eight anaplastic (ATC), and five medullary thyroid carcinomas (MTC), in addition to 35 samples of either follicular adenoma (FA) or normal thyroid tissue. Samples were reverse-transcribed and analysed using TaqMan polymerase chain reaction (PCR). TSHr expression was shown to be similar to normal in FA and inversely related to the grade of the majority of thyroid cancers other than MTC, in which, as expected, there was negligible expression. It is concluded that reduced expression of TSHr implies decreased responsiveness to TSH manipulation and is therefore a clinically important prognostic indicator in thyroid cancers.

Polypoid dermal hemangiopericytoma: a case report.

A polypoid dermal lesion with histologic, immunohistochemical, and ultrastructural features of hemangiopericytoma is described. Such tumors, arising in the dermis, are exceptionally rare, and whereas the tumor bears some resemblance to meningioma-like tumors of the skin and the well-recognized animal counterpart, canine hemangiopericytoma, it is histologically distinct.

Mistletoe lectin I forms a double trefoil structure.

The quaternary structure of mistletoe lectin I (MLI), a type II ribosome inactivating protein, has been determined by X-ray crystallography. A definitive molecular replacement solution was determined for MLI using the co-ordinates of the homologue ricin as a search model. MLI exists as an [AB]2 dimer with internal crystallographic two-fold symmetry. Domain I of the B chains is non-covalently associated through interactions involving three looped chains (alpha, beta, gamma) in each molecule of the dimer, forming a double trefoil structure. The ricin molecule which shares 52% sequence homology with MLI has a disulphide bridge between Cys20 and Cys39 in the alpha loop. An evolutionary mutation has replaced Cys39 with serine in MLI. This mutation appears to allow the alpha loop the flexibility required to take up its place at the dimer interface, and also suggests a rationale for why ricin does not form dimers. Measurement of retention times using FPLC gel filtration confirms that dimerisation also occurs in solution between MLI B chains with an association constant Ka = 10(6) M.

Preliminary crystallographic characterization of ricin agglutinin.

The quaternary structure of ricin agglutinin (RCA) has been determined by x-ray crystallography. The refined structure of ricin proved to be a successful search model using the molecular replacement method of phase determination. RCA forms an elongated molecule of dimensions 120 A x 60 A x 40 A with two A chains at the center and a B chain at each end. The A chains are covalently associated via a disulfide bridge between Cys 156 of both chains. Additional contacts at residues 114-5 stabilize the dimer interface. The covalent association of RCAA chains was confirmed by gel filtration under reducing and nonreducing conditions.

Sudden death in Whipple's disease.

Despite antibiotic therapy, some patients with uncomplicated Whipple's disease die suddenly and inexplicably. We describe one such patient who died following unexplained cardiorespiratory arrest and was found to have chronic active myocarditis related to the causative organism. We postulate myocarditis as a cause of sudden death.

Disseminated herpes zoster in the elderly.

We describe three cases of disseminated herpes zoster occurring in the elderly, and discuss the investigation and diagnosis of this condition. The presentation may be atypical with excoriated papular lesions. We suggest that disseminated herpes zoster does occur in the non-immunocompromised elderly patient, and is sometimes overlooked.

Myocarditis in Whipple's disease: an unsuspected cause of symptoms and sudden death.

Whipple's disease (WD) is an uncommonly diagnosed infection caused by the recently characterized bacillus, Tropheryma whippelii. The association of WD with pericarditis and endocarditis is widely recognized, although less attention has been paid to the myocardium as a site of disease. Although the disease was uniformly fatal before antibiotic therapy, current treatment usually results in cure. We report two patients whose deaths were directly related to cardiac involvement by WD and whose underlying disease escaped diagnosis for years. The first, a 60-year-old white woman, suffered a cardiovascular collapse, and lymphocytic myocarditis was demonstrated at autopsy. The second, a 48-year-old black man, had a lengthy history of progressive cardiac failure that terminated in arrhythmia. Extensive myocardial fibrosis, with lymphocytic and granulomatous inflammation, was demonstrated at autopsy. The presence of T. whippelii was confirmed by electron microscopic examination in both cases and by polymerase chain reaction in one. Patients with WD might harbor an undiagnosed lymphocytic or granulomatous myocarditis, and this diagnosis should be considered in the evaluation of cardiac failure.

Tumour related cutaneous elastophagocytosis.

Dermal granulomatous inflammation was identified immediately adjacent to seven (77%) of nine atypical fibroxanthomas arising in sun damaged skin. Concomitant elastophagocytosis was observed in five (56%) of these seven patients. Similar inflammation with elastophagocytosis was found in association with only two (6%) of 36 epithelial tumours arising on the same background (10 basal and 10 squamous cell carcinomas, 10 nodular malignant melanomas, and six keratocanthomas). Granulomatous inflammation is an unusual dermal reaction to tumour and elastophagocytosis is rare. The fact that both of these features occur with inordinate frequency in association with atypical fibroxanthomas, when compared with other, more common skin tumours, suggests that atypical fibroxanthomas might modulate the inflammatory response, either passively, by its dermal location, or actively, by secreting locally effective cytokines.

Pleomorphic adenoma of the bronchus.

An example of pleomorphic adenoma of the bronchus is described in a 27 year old male student who was referred for evaluation of a coin lesion identified incidentally on chest x ray. The tumour exhibited the classic histological, immunohistochemical and ultrastructural features of this rare entity but, in addition, contained mature and immature adipose tissue in the stroma and showed transition, in its superficial portion, between ostensibly normal bronchial mucus glands and tumour tubules. Neither of these features has been commented upon previously.

Recrudescence of Helicobacter pylori infection in patients with healed duodenal ulcer after treatment with different regimens.

OBJECTIVE: To determine the 12-month posttherapy recurrence (recrudescence) of Helicobacter pylori in patients with healed duodenal ulcer after apparent eradication of the organism with anti-H. pylori treatment. The influence of original anti-H. pylori treatment regimens on the recrudescence was also evaluated. METHODS: One hundred and ninety patients who had duodenal ulcer healed and H. pylori eradicated (as assessed by four routine techniques 4 wk after the end of anti-H. pylori therapy) with one of five regimens were studied. The five regimens were: 1) colloidal bismuth subcitrate (CBS) 120 mg; 2) CBS plus amoxicillin (500 mg); 3) CBS plus metronidazole (400 mg); 4) CBS plus metronidazole and amoxicillin; and 5) CBS plus metronidazole and tetracycline (500 mg). CBS was taken four times daily for 4 wk, and antibiotics were taken three times daily for the first week. The patients were re-endoscoped, and the status of H. pylori, duodenal ulcer, and gastritis was assessed after a period of follow-up (mean 14 months after commencement of treatment). RESULTS: H. pylori infection recurred in 36 (18.9%) of these patients. Recrudescence rate with monotherapy was 47.1%, with dual therapy 29.2-35% and with triple therapy 9.2-14.3%. Nineteen (52.7%) of the 36 patients with recrudescent infection had ulcer relapse, and the rate for H. pylori-negative patients was 3.2% (5/154). CONCLUSION: Recrudescence of H. pylori infection after apparent eradication can occur, but it could be that the treatment was only suppressing the organism. The definition of eradication of H. pylori infection may need to be revised, and more sensitive techniques to assess eradication of H. pylori are required.

Apoptotic and mitotic indices in malignant melanoma and basal cell carcinoma.

AIMS: To assess the relative frequency of mitotic and apoptotic cells in malignant melanoma and basal cell carcinoma. METHODS: Retrospective evaluation of haematoxylin and eosin stained slides from 10 basal cell carcinomas, 10 nodular melanomas, and 10 superficial spreading melanomas, with counting of apoptotic and mitotic cells per 1000 cells. Selected cases were studied with in situ end-labelling. RESULTS: The ratio of apoptotic to mitotic cells was higher in basal cell carcinoma than in either form of melanoma because of the presence of a greater number of apoptotic cells in basal cell carcinoma. CONCLUSION: The differing growth rates and biological behaviour of these two tumours is reflected in the apoptotic:mitotic ratio. Further assessment of this ratio is warranted, both between tumour types and between individual tumours of one type, to determine its value as an indicator of biological potential.

Chronic Brucella infection of the supra-patellar bursa with sinus formation.

A case of supra-patellar bursitis with the formation of discharging sinus is described. B abortus was isolated from resected bursal tissue. While osteoarticular complications of brucellosis are common and a number of different clinical syndromes are now recognised, disease of the bursae is rare and as far as is known sinus formation has not been described before in this setting.