Reduction of proteinuria with mycophenolate mofetil in predominantly membranous lupus nephropathy.

INTRODUCTION: Lupus membranous nephropathy (LMN) presents a difficult clinical problem as no particular treatment has been proven to be effective. Studies have shown good results with mycophenolate mofetil (MMF) in proliferative lupus nephropathy (LN) (WHO class III and IV disease). OBJECTIVES: To study whether MMF treatment was effective in membranous predominant LN in patients resistant to or intolerant of other immunosuppressive agents. PATIENTS AND METHODS: We retrospectively studied 10 patients with systemic lupus erythematosus who had biopsy-proven predominant LMN (six Vc patients and four Va or Vb patients). Previous treatments included cyclophosphamide, azathioprine, ciclosporin and corticosteroids. The following parameters were recorded at baseline and follow-up: blood pressure, ECLAM, proteinuria, serum albumin and creatinine, routine haematology and immunology. RESULTS: The study included eight women and two men, mean age 38.4 +/- 7.1 yr (range 30-49 yr). The racial distribution was as follows: five Caucasian, and five Black patients. The mean treatment time with MMF was 18.8 +/- 15.4 months (range 3-52 months). Twenty-four-hour urinary protein excretion was reduced from median 2.26 g (range 0-7.92 g) to median 0.66 g (range 0.08-3.85 g) at follow-up (P = 0.0039). Serum albumin increased significantly after treatment from median 29.5 g/l (range 14.0-42.0 g/l) to 33.5 g/l (range 23.0-40.0 g/l) at follow-up (P = 0.04). There were no significant changes in serum creatinine (P = 0.55). CONCLUSION: MMF is a potentially useful immunosuppressive agent in reducing the proteinuria associated with membranous predominant LN.

Mesenchymal chondrosarcoma of the thyroid -- a rare tumour at an unusual site.

We describe the light microscopic, immunohistochemical and ultrastructural features of the first case in the literature of a primary mesenchymal chondrosarcoma (MC) of the thyroid and discuss its differential diagnosis at unusual extraskeletal sites. A nodular lesion of the thyroid with no evidence of extrathyroid disease showed the bimorphic pattern and haemangiopericytoma-like areas typical of MC. In the undifferentiated areas, the cells were CD99 positive/CD117 negative, while the stroma showed focal positivity for alpha-inhibin. In spite of its rarity, it is important to diagnose primary mesenchymal chondrosarcoma in a parenchymatous organ such as the thyroid because its biological behaviour may be different from that of tumours of similar morphology and complete resection is the treatment of choice. The patient is free of disease nearly 66 months after its first presentation. Cytogenetic and immunohistological markers may play important roles in diagnosis of this lesion in future, especially with limited tissue samplings; however, for the present a thorough sampling of the tumour remains the best diagnostic strategy.

Angina with a normal coronary angiogram caused by amyloidosis.

A case of severe intractable angina pectoris with normal angiography is presented. Following video assisted thoracic sympathectomy the patient died of heart failure. Microvascular cardiac amyloidosis was diagnosed at the postmortem examination. This report alerts clinicians to this possible diagnosis when treating patients with severe angina when no cause is found and discusses the poor prognosis in such cases.

Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. OBJECTIVE: To study the immunological and demographic factors associated with the development of LN. PATIENTS AND METHODS: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. RESULTS: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. CONCLUSIONS: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN.

Hypertension as the presenting feature of the antiphospholipid syndrome.

The antiphospholipid or Hughes syndrome is the association between antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy morbidity. Antiphospholipid syndrome (APS) commonly coexists with autoimmune diseases usually systemic lupus erythematosus (SLE), when it is known as secondary APS. When present in isolation it is known as primary APS (PAPS). Although the kidney may be affected in APS, its involvement is perhaps not as well described as that of other organs. Thrombotic microangiopathy (TMA) affecting the kidney has been reported as a manifestation in both primary and secondary APS. This report describes hypertension related to underlying renal TMA as a presenting symptom of APS.

Pulmonary echinococcosis with chest wall involvement in a patient with no apparent risk factors.

Pulmonary hydatid disease is rare in the U.K., and chest wall involvement has to our knowledge not previously been described in this country. We report the case of a 72-year-old man who was found to have a left upper lobe opacity on his chest radiograph. He declined further investigation at the time, but 2 years later developed a palpable mass over his left lateral chest wall. Fine-needle aspiration-biopsy of this mass revealed the diagnosis of pulmonary hydatid disease. Despite thorough questioning, no risk factor could be identified for the development of the disease. Hydatid disease should be remembered as a rare cause of mass lesions identified on chest radiographs even in non-endemic regions. Spread to the chest wall may mimic malignancy.

Lymph node cytology in Wegener's granulomatosis.

We report on cytological findings on aspirates from the cervical lymph node from a case of Wegener's granulomatosis (WG). The diagnostic utility of technique in diagnosing a sizable minority of WG patients who present with cervical lymphadenopathy is discussed. We outline an approach to diagnosis of necrotising granulomatous lesions in aspirates from lymph nodes in a tabular form.

Tracheocarotid artery fistula infected with methicillin-resistant staphylococcus aureus.

Massive life-threatening haemorrhage from a fistula between the trachea and a major blood vessel of the neck is a rare complication of the tracheostomy procedure, well-recognized by anaesthetists and otolaryngologists. Although the lesion is likely to be encountered at autopsy, it is not described in histopathological literature. The possible causes are discussed together with the macroscopic and microscopic appearances of the lesion. Suitable procedures for its identification and for obtaining appropriate histopathological blocks are suggested. Presence of methicillin-resistant Staphylococcus aureus (MRSA) has not been documented before and might have contributed to the genesis of the fistula in this case.

Patterns of expressions of transforming growth factor and epidermal growth factor receptor in squamous cell lesions of the urinary bladder.

AIM: To investigate the patterns of expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in squamous metaplasia and squamous cell carcinomas of the urinary bladder with and without schistosomiasis. METHODS: Immunohistochemical study of the expression of TGF-alpha and EGFR in squamous metaplasias (n = 12) and various grades of squamous cell carcinomas (n = 21) of the bladder with and without schistosomiasis. RESULTS: Focal cytoplasmic and membranous positivity for EGFR and TGF-alpha was seen in all cases of squamous metaplasia. The markers were diffusely coexpressed in a concordant pattern in areas of hyperplastic keratinising squamous metaplasia. A similar pattern of positivity was seen in verrucous carcinomas (n = 2) and well differentiated squamous carcinomas (n = 6). Progressive loss of differentiation was associated with increasing loss of EGFR staining while TGF-alpha staining was retained. Squamous cell carcinoma in situ (n = 2) showed focal positivity for TGF-alpha and EGFR. There were no differences in staining patterns between cases with and without schistosomiasis. CONCLUSIONS: The coexpression of TGF-alpha and EGFR by well differentiated squamous cell carcinomas and hyperplastic keratinising squamous metaplasia is consistent with the active regulatory role exerted by this autocrine loop. There is regional absence of expression of EGFR but not of TGF-alpha in squamous cell carcinomas of lesser differentiation, suggesting heterogeneity of such control in these tumours. The focal expression of the two markers in squamous cell carcinomas in situ indicates a possible second pathway of oncogenesis for less differentiated tumours. These observations may have important implications for the effectiveness of putative growth factor based treatments.

Immunosuppressive therapy in lupus nephritis.

OBJECTIVE: To evaluate the outcomes and side effects of immunosuppressive therapy in patients with lupus nephritis. PATIENTS AND METHODS: Thirty-nine patients with lupus nephritis assessed between 1988 and 1993 with a median follow-up of 46 months (range 12-60 months) were studied. Lupus nephritis was biopsy-proven in 37 patients. Patients received a median of 3 (500 mg) weekly pulses of intravenous cyclophosphamide followed either by azathioprine (n = 32) or oral cyclophosphamide (n = 7). All patients received oral prednisolone. The time from biopsy to renal insufficiency, defined by doubled serum creatinine and/or end stage renal failure, was used to assess outcome. RESULTS: There were significant improvements in the median changes of all major laboratory parameters. Serum creatinine levels did not change significantly. The prednisolone dose was significantly reduced during the follow-up period. OUTCOME: renal function remained stable in 26 (67%) and deteriorated despite therapy in 13 (33%) patients. 6/13 (42%) of these patients had impaired renal function at the time of biopsy. The adverse effects of intravenous cyclophosphamide seen were Herpes zoster (1), transient leucopenia (2), rash (1) and fatal septicaemia (1); of azathioprine urinary infections (3), leucopenia (5), rash (1) and increased liver enzymes (1); and of oral cyclophosphamide ovarian failure (4), Herpes zoster (3), haemorrhagic cystitis (1), and fatal septicaemia (1). CONCLUSIONS: Therapy with weekly low dose intravenous pulse cyclophosphamide to induce remission, followed by azathioprine appears to be useful in preserving renal function in patients with diffuse proliferative lupus nephritis. In comparison to other studies, the reduced incidence of ovarian failure using this regimen was striking.

Glomerular basement membrane thickness - a comparison of two methods of measurement in patients with unexplained haematuria.

BACKGROUND: Thin glomerular basement membranes may be an important cause of microscopic haematuria. Unfortunately measurements are often not made because of the complicated methods currently employed. METHODS: A simplified method of measurement of glomerular basement membrane thickness, involving only 16 selected measurements on a single glomerulus, was compared with the accepted, but time-consuming, orthogonal intercept technique. Thirty-one needle biopsies from patients with renal haematuria unexplained by conventional histology and immunofluorescence were studied. Measurements were made on the same ultrathin sections. RESULTS: The new method was found to give much lower values (mean (SD) 202+/-51 versus 282+/-52 nm) with limits of agreement of -131 to -30 nm compared with the orthogonal intercept method. The coefficient of repeatability was 39 nm for the orthogonal intercept method and 56 nm for the new method. However, using two glomeruli the new method had limits of agreement of -120 to -41 nm with a coefficient of repeatability of 38 nm. CONCLUSIONS: Provided two glomeruli are measured the new technique is sufficiently accurate for the diagnosis of thin membrane nephrology, in appropriate cases, and is much simpler and cheaper than the orthogonal intercept method.

Bladder carcinomas and normal urothelium universally express gp200-MR6, a molecule functionally associated with the interleukin 4 receptor (CD 124).

Monoclonal antibody MR6 detects gp200-MR6, a molecule functionally associated with the interleukin 4 (IL- 4) receptor. Positive immunolabeling with MAb MR6 was obtained in 28/28 transitional cell carcinomas of the bladder, representing a range of different grades and stages of disease, as well as in all control non-neoplastic urothelia. The expression of mutant p53 protein and epidermal growth factor receptor was detected in 14/28 and 20/28 cases respectively. Proliferation indices, determined by Ki67 labeling, ranged from 5% to 95% among these tumours. The universal expression of gp200-MR6 in neoplastic and non-neoplastic urothelium has important implications for the possible use of IL-4 in tumour therapy and suggests that IL- 4 may play a role in differentiation and homeostasis of urothelium and other mucosal epithelia.

Schwannoma of the external auditory canal.

Solitary schwannomas are relatively rare. There has been only one previously reported case, in the English literature, of a schwannoma arising in the external auditory canal. We present a case which was managed by local excision and was unassociated with cochlear or retrocochlear pathology.

Carcinoma of the parotid gland presenting as facial pain.

Facial pain is a common reason for patients seeking medical help. A patient is presented who gave a 5-month history of right-sided facial pain, which was subsequently diagnosed as carcinoma of the right parotid gland.

bcl-2 protein in non-small-cell lung carcinoma.

BACKGROUND: The proto-oncogene bcl-2 encodes a protein that inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but no data are available on the frequency or clinical importance of its expression in carcinoma. We studied bcl-2 expression in patients with non-small-cell lung carcinoma and correlated this phenomenon with survival. METHODS: Immunochemical analysis with a monoclonal antibody specific for bcl-2 was used to detect the protein in tumor samples from 122 patients undergoing surgery for squamous-cell carcinoma (80 patients) or adenocarcinoma (42 patients). The possibility that bcl-2 expression correlated with survival was investigated with use of the log-rank test, hazard ratios, and their confidence intervals. RESULTS: We detected bcl-2 protein in 25 percent of squamous-cell carcinomas (20 of 80) and 12 percent of adenocarcinomas (5 of 42). In adjacent normal respiratory epithelium, bcl-2 was expressed only in basal cells. Survival at five years was higher among patients with bcl-2-positive tumors, both in the group as a whole (P < 0.1) and in the group with squamous-cell carcinoma (P < 0.02). Patients 60 years of age or older who had bcl-2-positive tumors had the best prognoses, both in the group as a whole (P < 0.02) and in the group with squamous-cell carcinoma (P < 0.01). CONCLUSIONS: The proto-oncogene bcl-2 is abnormally expressed in some lung carcinomas, and its expression may have prognostic importance.