IMP3 staining is not a useful marker for adrenocortical carcinoma

ABSTRACTS

gland, and to discuss the differentials and potential diagnostic pitfalls. Method and result: An excision from a 45-year-old Caucasian man presenting with a lump on his left finger was routinely processed and examined. The tumour was composed of cystic spaces displaying tubulo-alveolar growth and some papillary projections protruding into the cystic lumina, outlined by thick fibrous tissue. The cells displayed a relatively even nuclear chromatin pattern, smooth nuclear outlines, with occasional nucleoli and abundant mitoses with focal squamous metaplasia. A diagnosis of aggressive digital papillary adenocarcinoma was made. Discussion: This entity is a rare neoplasm of eccrine sweat gland origin which typically presents as a mass on a finger. The majority of these cases occur in males in their 5th–7th decade, and less than 100 cases have been reported. MALIGNANT MELANOCYTIC MATRICOMA: A CASE REPORT AND REVIEW OF THE LITERATURE K. Limarporn, R. Lourie, L. Pool, D. Wong Pathology Department Princess Alexandra Hospital, Pathology Queensland, Woolongabba, Qld, Australia Aim: To describe and review literatures for malignant melanocytic matricoma and, to discuss the differentials and potential diagnostic pitfalls. Method: A skin excision from an 81-year-old man presenting with a skin lesion was processed routinely and examined, including several immunohistochemical studies, namely AE1/AE3, S-100, and MelanA. Result: The tumour was characterised by an exophytic nodular growth with ulceration displaying biphasic features, and composed of both basaloid cells and larger pigmented melanocytic cells. Pigmentation was variable, with dendritic cells noted. Up to 20 mitoses/10 HPF were observed. The small basaloid tumour cells were positive for AE1/AE3, and the larger tumour cells were positive for S-100 and MelanA. Discussion: This entity is a malignant neoplasm with hair matrix and hair differentiation. The histological criteria in favour of malignancy include infiltrative growth, numerous mitotic figures, abnormal mitoses, nuclear atypia, loss of ghost cells at the advancing edge, lymphatic and blood vessel invasion, perineural invasion, local recurrence and lymph node or visceral metastases. DIFFERENCES IN BIOLOGY OF COLORECTAL CANCER SUBTYPES WITH MUTANT TGFBR2 AND SMAD4 Grace Liu, Nicholas Fleming, Lara Lipton, Oliver Sieber Ludwig Colon Cancer Initiative, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, and Cabrini Health, Malvern, Vic, Australia Aim: The TGF-b signalling pathway is principally composed of the TGF-b receptors (including TGFBR2) and the SMAD family signalling factors, and is implicated in the control of epithelial mesenchymal transition (EMT). In colorectal cancer, SMAD4 and TGFBR2 are mutated in approximately 15% and 10%, respectively. We hypothesised that cancers harbouring these gene mutations would differ in their biology and perhaps thus clinical progression. Methods: Ten cancers with biallelic mutation of TGFBR2, ten with biallelic mutation of SMAD4 and ten wildtype for the two genes were assessed for tumour budding and E-cadherin

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expression. Tumour sections were stained with H&E, AE1/3 and immunohistochemistry for E-cadherin. Staining intensity and percentage of cell positivity were scored and compared between the three groups. Results: Tumour budding was lower in TGFBR2 mutant cancers than the SMAD4 and WT groups when stained by H&E ( p < 0.05). The percentage of cells staining positive for E-cadherin was significantly higher in the SMAD4 mutant cancers than the TGFBR2 mutant set ( p < 0.028), but the difference in intensity was not significant. Conclusions: These data suggest that the mutation status of the TGF-b pathway may correlate with colorectal tumour biology and is potentially relevant to clinical progression and metastatic spread. These results warrant further investigation. GENETIC VARIATION ASSOCIATED WITH THE IL28B GENE PREDICTS ALLERGIC DISEASE Michaela Lucas1,3, Silvana Gaudieri2,3,4, Andrew Lucas3, Elizabeth McKinnon3, Hiba Albloushi4, Andri Rauch5, Julia di Iulio6, David Martino7, Susan L. Prescott7, Meri K. Tulic7 1 Department of Immunology, PathWest, Fremantle Hospital, WA, 2 School of Anatomy and Human Biology, University of Western Australia, WA, 3Institute for Immunology and Infectious Diseases (IIID), Murdoch University, WA, 4Centre for Forensic Science, University of Western Australia, WA, Australia, 5University Clinic of Infectious Diseases, University Hospital Bern and University of Bern, Switzerland, 6Institute of Microbiology, University Hospital Centre and University of Lausanne, Switzerland, and 7School of Paediatrics and Child Health, University of Western Australia, WA, Australia; the majority of the work was performed at IIID, Murdoch University Background: Environmental changes influencing the interaction between the maturing immune system and pathogen exposure are implicated in the rising rates of allergic disease. There is emerging evidence that differences in innate immune function contribute to the development of allergy. Consequently, associated genetic factors may be critical for the difference in immune ontogeny, seen in allergic children. Aims: We examined if genetic variation associated with the IL28B gene, encoding for the potent immune modulator IFN lambda 3, contributes to the divergent immune response in selected children who were followed from birth to 5 years of age (35 allergic and 35 non-allergic children). Results: We found that carriage of the T allele of the SNP rs12979860, tagging the IL28B gene, is significantly associated with allergy ( p ¼ 0.004; OR 4.56). This association increases with age and is particularly evident in girls (OR 16). In addition, variation at rs12979860 correlates with differences in the proinflammatory profile (IL1B production) at birth after TLR stimulation of cord blood cells. Conclusion: In the context of rising rates of disease, the genetic variation described may contribute to key differences in innate immune development of allergic children and points towards a role of IFN lambda III in allergic disease pathogenesis. IMP3 STAINING IS NOT A USEFUL MARKER FOR ADRENOCORTICAL CARCINOMA H. M. Manuchehri, A. Clarkson, L. Siosson, A. J. Gill Royal North Shore Hospital, Sydney, NSW, Australia

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PATHOLOGY 2012 ABSTRACT SUPPLEMENT

Adrenocortical carcinoma (ACC) is a rare tumour with challenging pathological diagnosis. The Weiss scoring system which is based on the recognition of at least three of nine morphological parameters is the most widely used criteria. However the Weiss system is not entirely sensitive or specific, and some of the criteria are subjective and potentially problematic. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC. Alterations of the insulin-like growth factor-II (IGF-2) molecule seem to be promising particularly when used in conjunction with Ki67 index. The insulin-like growth factor-II mRNAbinding protein (IMP3) has been shown to be a useful marker of malignancy in multiple organs. We investigated IMP3 expression by immunohistochemistry in TMAs of 35 ACCs and 161 adrenal cortical adenomas. IMP3 immunoreactivity was seen in two (6%) ACC and in none of the adrenal cortical adenomas. We conclude that despite its high specificity for the diagnosis of malignancy in adrenal cortical neoplasms, its very low sensitivity means IMP3 overexpression is unlikely to be useful in the diagnostic setting. References 1. Findeis-Hosey JJ, H Xu H. The use of insulin like-growth factor II messenger RNA binding protein–3 in diagnostic pathology. Hum Pathol 2011; 42: 303–14. 2. Volante M, Buttigliero C,Greco E, et al. Pathological and molecular features of adrenocortical carcinoma: an update. J Clin Pathol 2008; 61: 787–93. 3. Soon PS, Gill AJ, Clarkson, et al. Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas. Endocr Relat Cancer 2009; 16: 573–83.

STIR: A STATE APPROACH TO HAEMOVIGILANCE Ellen Maxwell on behalf of the Blood Matters Serious Transfusion Incident Reporting Expert Group, Blood Matters Program, Department of Health Victoria and the Australian Red Cross Blood Service Background/aim: Serious Transfusion Incident Reporting system (STIR) is the voluntary haemovigilance framework developed by Blood Matters program for Victoria, on behalf of the Department of Health and the Blood Service. It was developed in 2005 to capture serious transfusion incidents, including near misses. It provides a central system for reporting events related to administration and handling of fresh blood components and pre-transfusion samples. Method: Health services submit initial notifications and the STIR office provides follow-up forms relevant to the event type (e.g., incorrect blood component transfused, IBCT) for completion. Information (de-identified) regarding the case is returned for data entry and review, including attribution of causality and severity, by an expert clinical group. STIR links with the Victorian Department of Health sentinel event program, where it is mandatory to report ABO incompatible transfusion events. Results: Participation to date is 71 public and private hospitals and laboratories, across four jurisdictions (Victoria, Tasmania, Australian Capital Territory and Northern Territory). To date there have been 946 transfusion adverse events in 939 patients (both adults and children) notified. Conclusion: STIR continues to evolve in its processes for transfusion data reporting while ensuring it provides ongoing feedback to those reporting and derives recommendations for better, safer transfusion practice. LYMPHANGIOLEIOMYOMATOSIS OF THE LUNG WITH CONCURRENT PULMONARY AND RENAL ANGIOMYOLIPOMATA: A UNIQUE CASE Mikkaela McCormack, Catriona McLean

Pathology (2012), 44(S1)

Department of Anatomical Pathology, The Alfred Hospital, Prahran, Vic, Australia We present a unique autopsy case of a 61-year-old female with concurrent renal and multi-focal pulmonary angiomyolipomata (AML) in the setting of pulmonary lymphangioleiomyomatosis (LAM), and in the absence of documented tuberous sclerosis. There are no previously reported cases of pulmonary AML in the setting of LAM. The patient had undergone single lung transplantation 12 months prior to presenting with severe acute fibrinoid organising pneumonia in her donor lung. Despite full treatment she died 3 months following admission. Imaging revealed multiple tumours in the right kidney and left retroperitoneum, consistent with large angiomyolipomata. A left nephrectomy for a ‘benign tumour’ was performed 45 years previously. Limited post-mortem examination of the native lung revealed marked cystic change and two 3 mm homogenous yellow parenchymal nodules. Histological examination showed cystic dilatation and a patchy proliferation of interstitial human melanoma black 45 (HMB45)-positive spindled cells consistent with LAM. The nodules were well-circumscribed, composed of mature adipocytes, small blood vessels and bland spindled cells with occasional epithelioid forms exhibiting positive staining with HMB45, smooth muscle actin and myosin, consistent with a diagnosis of AML. On review, these lesions were not seen on repeated antemortem imaging. This case illustrates that pulmonary lesions morphologically and immunohistochemically identical to AML can rarely co-exist with LAM and renal AML, and that they may be small, multiple and undetectable by imaging. We recommend that all lungs with known or suspected LAM be carefully examined for such lesions. PLASMA LEVELS OF JC VIRUS ARE SENSITIVITY AND SPECIFIC FOR DETECTING AND PREDICTING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY IN HIV PATIENTS Julianne Bayliss1, Catherine L. Cherry1,2,3, Catriona A. McLean1,4 1 Department of Medicine, Monash University, Alfred Hospital, Melbourne, 2Centre for Virology, MacFarlane Burnet Institute, Melbourne, 3Infectious Diseases Unit, Alfred Hospital, Melbourne, and 4Anatomical Pathology, Alfred Hospital, Melbourne, Vic, Australia Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC virus (JCV) reactivation with a high mortality and no definitive treatment. HIV-1 infection represents the most common underlying immunosuppressive condition associated with PML. Methods: Nested PCR (nPCR) and real time PCR (qPCR) for JCV DNA was performed on serial plasma samples obtained from 14 HIV patients with a clinical diagnosis of PML and 27 controls (HIV patients without PML matched to cases on CD4 count, viral load, and treatment status). Results: nPCR detected JCV LT DNA in 4/14 (29%) PML cases at disease onset but no controls ( p ¼ 0.003). JCV LT DNA was detected via qPCR in 11/14 (78%) PML patients at disease onset and 4/27 (15%) controls ( p < 0.001). The availability of plasma samples collected prior to PML diagnosis allowed a preliminary evaluation of the predictive utility of JCV LT qPCR. Logistic

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