Paul R. McKenzie

Thymoma: trends over time

BACKGROUND This is a review of a series of patients who presented with thymoma over the most recent 20-year period. Changes and trends in disease patterns were documented. METHODS Data were collated retrospectively but all pathology slides were reviewed. Survival functions were estimated using the Kaplan-Meier method. RESULTS Seventy-one patients had a partial or total thymectomy during this period for a thymoma. Average age was 55 years. Twenty-three patients (32%) had myaesthenia gravis. Eighteen patients (25%) were asymptomatic. Thirty-three patients (47%) had stage 1 disease. Complete resection was achieved in 60 patients (85%). Five-year survival was 88%. Fifty percent of patients with myesthenia gravis showed improvement in symptoms. CONCLUSIONS Five- and 10-year survival rates in this study are better than in other series. We attribute this to an increasing number of patients with stage 1 and stage 2 disease, particularly those with myasthenia gravis who now have screening computer tomography, and also to the surgical intent of aiming to achieve complete resection even if excision of adjacent tissue is required.

Tenofovir-associated Fanconi syndrome in patients with chronic hepatitis B monoinfection.

Tenofovir disoproxil fumarate (TDF) is increasingly used in patients with chronic hepatitis B (CHB) infection. Although associated with renal toxicity in HIV-infected patients, renal dysfunction has been reported rarely in the monoinfected CHB population. To date, TDF-associated Fanconi syndrome has not been reported. Here, we present two cases of TDF-associated Fanconi syndrome with rapid resolution after its cessation. We then discuss risk factors for TDF nephrotoxicity and its implications for screening for renal disease in those patients with CHB monoinfection on TDF, and the use of TDF in at-risk populations.

Diagnosis of metastatic melanoma by fine-needle biopsy : Analysis of 2,204 cases

Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases.

Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas).

Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-α for 2weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-α infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-α treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-α can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control.

Diagnostic Accuracy of Fine Needle Biopsy for Metastatic Melanoma and Its Implications for Patient Management

BackgroundThe use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated.MethodsA retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up.ResultsFNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results.ConclusionsFNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma.

Photopheresis therapy for problematic renal allograft rejection.

Background: Photopheresis is an immunomodulatory therapy for the treatment of T cell‐mediated disorders. It has been used for rejection prophylaxis in cardiac transplantation, adjuvant treatment of bronchiolitis obliterans in lung transplantation, treatment of graft verse host disease, and in a small number of cases, for treatment of acute rejection in renal transplantation. Little is known of long‐term outcomes following the use of photopheresis in solid organ transplantation. Methods: We report prospective follow‐up of our consecutive experience of the use of photopheresis as adjuvant/salvage therapy for problematic rejection in patients undergoing renal transplantation. Transplant graft survival, infective and malignant outcomes were reported. Results: A cohort of 10 renal transplants recipients received photopheresis therapy for therapy‐resistant rejection. Conventional therapy included an average of 6.2 g pulse methyl‐prednisolone and 17.1 days antilymphocyte therapy. The cohort received additional photopheresis therapy when the unresponsive nature of their rejections raised concerns of graft loss. Median follow‐up censored for patient loss was 66.7 months following photopheresis commencement. Rejection resolved in association with photopheresis use in all 10 patients. Six patients continued to have stable graft function (median serum creatinine: 191.5 μmol/L) at a median follow‐up of 71.0 months. There has been one patient death from sepsis and two from malignancy with functioning grafts while one graft has been lost to disease recurrence. Conclusion: Photopheresis may have a role as an adjuvant or salvage antirejection therapy in solid organ transplantation. Furthermore, evaluation in randomized controlled clinical trials is required to evaluate its potential. J. Clin. Apheresis, 2009.

Her2 Testing recommendations in Australia

Summary HER2 is the target of a new treatment for metastatic breast cancer using the humanised monoclonal antibody trastuzumab (Herceptin). Since only around 20% of breast cancers carry the overexpressed HER2 receptor protein to which this treatment is directed, patient selection is very important in determining eligibility for the drug. Currently, immunohistochemistry and fluorescence in situ hybridisation are the main tests used for HER2 detection, and these testing recommendations have been developed based on national and international data.

Acute oxalate nephropathy secondary to orlistat-induced enteric hyperoxaluria.

1. BBraun. Gelofusine product information. [Cited 10 July 2012.] Available from URL: http://www.bbraun.com 2. de Keijzer MH, Klasen IS, Branten AJ, Hordijk W, Wetzels JF. Infusion of plasma expanders may lead to unexpected results in urinary protein assays. Scand. J. Clin. Lab. Invest. 1999; 59: 133–7. 3. Jones CM, Sumeray M, Heys A, Woolfson RG. Pseudo-proteinuria following gelofusine infusion. Nephrol. Dial. Transplant. 1999; 14: 944–5. 4. Pena C, Martinez-Bru C, Homs R, Planella T, Cortes M. Effect of plasma replacement therapy on determinations of urine protein concentration. Clin. Chem. 1998; 44: 359–60. 5. Lazard T, Deswartes-Pipien I, Tenenhaus D et al. [Proteinuria after infusion of gelatin. Comparison of Plasmion and Haemaccel]. Therapie 1989; 44: 269–74.

Melanotic schwannoma mimicking metastatic pigmented melanoma: a pitfall in cytological diagnosis

Sir, Melanotic schwannomas are rare tumours and less than 100 cases have been reported in the literature. In 40–50% of cases psammoma bodies are identified and these tumours have been termed ‘psammomatous melanotic schwannomas’. Melanotic schwannomas are a component of Carney’s complex, a syndrome in which patients manifest myxomas, spotty pigmentation (lentigenes and epithelioid blue naevi/pigmented epithelioid melanocytomas) and endocrine hyperactivity, along with a variety of other tumours including large cell calcifying Sertoli cell tumours, thyroid tumours and ductal adenomas of the breast. Melanotic schwannomas occur most commonly in a paraspinal location, but may also arise in the oral cavity, skin, soft tissue, bone and the gastrointestinal tract. The fine needle biopsy (FNB) features of melanotic schwannomas have been rarely reported. We describe the cytological features of a case of melanotic schwannoma which resembled metastatic melanoma. A 31-year-old woman presented with an incidentally discovered right paravertebral retroperitoneal mass. She had a previous history of a Hurthle cell tumour of the thyroid gland. On imaging, the mass was well circumscribed and measured 256 206 20 mm. A computed tomographyguided FNB was performed. The FNB smears showed small syncytial tissue fragments and sheets composed of pleomorphic elongated spindle shaped and ovoid cells containing abundant cytoplasmic pigment associated with plentiful pigment-laden macrophages (Fig. 1A–C). Similar single cells were also present, with considerable pigment and necrotic material in the background. The N:C ration varied from low to high, and the nuclei were large, highly pleomorphic with coarse chromatin, large nucleoli and some nuclear pseudoinclusions. The pigment was finely to coarsely granular, brownish-black in colour, and positive with Schmorl’s stain, consistent with melanin. Immunohistochemistry was performed (using alkaline phosphatase and a red chromogen) and showed that the tumour cells were positive for S100 (Fig. 1D), HMB-45 and Melan-A as well as neuron specific enolase (NSE). Cytokeratin, chromogranin and synaptophysin were negative. The FNB findings were initially interpreted as representing metastatic melanoma. Subsequently the FNB slides were reviewed and reinterpreted as typical but not diagnostic of metastatic melanoma. While it was considered that metastatic melanoma remained in the differential diagnosis, other primary retroperitoneal pigmented tumours such as pigmented schwannoma, malignant peripheral nerve sheath tumour and a germ cell tumour exhibiting retinal differentiation could not be excluded purely on the basis of the cytological features. This was particularly in view of the young age of the patient, the presentation in a relatively uncommon site for metastatic melanoma, absence of a prior history of

Cytological features of melanoma in exfoliative fluid specimens

Aims: To describe the cytological appearances of melanoma in fluid specimens and potential diagnostic pitfalls in interpreting such specimens, which have been infrequently reported in the literature. Methods: Cases of melanoma diagnosed at a single institution between 1993 and 2008 in cytology specimens of fluids (pleural, ascitic, cerebrospinal and other fluids), but excluding fine needle biopsy specimens, were identified and reviewed. Results: 32 fluid specimens containing metastatic melanoma (from 26 patients) were identified. Most of the specimens were moderately cellular and showed moderate to marked nuclear pleomorphism. Mitotic figures and intranuclear cytoplasmic invaginations were identified in 11 (34.4%) and seven (21.9%) cases, respectively. Melanin pigment was seen in eight (25.0%) cases. Variable numbers of histiocytes were present, and mesothelial cells were present in body cavity fluid specimens. Conclusions: In fluid specimens, reactive mesothelial cells and histiocytes may mimic epithelioid melanoma cells. Awareness of the morphological features and diagnostic pitfalls of melanoma in fluids is necessary to avoid the potentially serious consequences of misdiagnosis.