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The combination of FISH and IHC for ALK assessment in NSCLC is more powerful than either technique alone
ABSTRACTS
COLORECTAL ADENOCARCINOMA WITH THE SERRATED NEOPLASIA PATHWAY Renn Montgomery and Tao Yang Department of Anatomical Pathology, Liverpool Hospital, Liverpool, NSW, Australia The conventional pathway for the development of colorectal carcinoma (CRC) has been well described, and involves mutations in the APC gene, as well as alterations in p53 and the development of microsatellite instability. A more recently described pathway implicates sessile serrated lesions in the development of colorectal carcinoma, illustrated by a case we report of a 66-year-old male presenting with three synchronous adenocarcinomas, with multiple sessile serrated adenomas (SSAs). BRAF V600E mutation was detected and there was sporadic microsatellite instability. The serrated neoplasia pathway differs from the conventional pathway, involving mutations in the BRAF oncogene, as well as epigenetic mechanisms leading to abnormal hypermethylation of tumour suppressor genes. This methylation may involve MLH1, leading to sporadic microsatellite instability, as seen in our case. Sessile serrated lesions are the precursor for this pathway, and it is possible that they may progress to carcinoma more rapidly than conventional adenomas. They are often difficult to identify and completely remove. Thus, screening of SSAs and identification of SSA polyposis to prevent CRC may be of particular clinical significance.
THE COMBINATION OF FISH AND IHC FOR ALK ASSESSMENT IN NSCLC IS MORE POWERFUL THAN EITHER TECHNIQUE ALONE A. L. Morey, B. Brown, D. Riley, G. Gracie and M. R. Qiu Department of Tissue Pathology and Cancer Genetics, SydPath, St Vincent’s Hospital, Darlinghurst, Sydney, NSW, Australia Aim: Examination of the proposition that detection of ALK overexpression by IHC in NSCLC may act as triage or replacement for FISH. Method: Results on 221 NSCLCs referred for ALK FISH testing (Abbott-Vysis LSI ALK Breakapart FISH Probe) were reviewed, FISH hybridisation pattern classified and compared to ALK IHC (Clone D5F3). Results: 10 cases (4.5%) had insufficient material for testing. Thirty-four cases were FISH þ ve, four equivocal (1.8%) and 173 negative. Seventeen positive cases had classic ‘split’ signal; 14 had isolated 3’ red signals, two had combined pattern and two cases (both IHC þ ve) had variant patterns with additional 5’ (green) signals (previously regarded as FISH–ve). Twenty-nine of these 34 cases were IHC þ ve (85% IHC sensitivity), three were IHC equivocal, 1 was untested, and 1 IHC–ve. Two FISH equivocal cases (minimal split) were strongly IHC þ ve. One of 173 FISH–ve cases was strongly IHC þ ve. IHC on 196 cases scored 32 as positive, 14 equivocal (7%) and 150 negative. 25 IHC þ ve cases were straightforward FISH þ ve, six had variant/equivocal FISH patterns, one was FISH–ve (97% IHC specificity). Three of 14 IHC equivocal cases were FISH þ ve, as was one IHC–ve case. Discussion: Combination of IHC and FISH for detection of ALK mutation is more powerful than either test in isolation. Without availability of IHC, six cases with equivocal or variant FISH patterns would likely have been missed, however four times more cases are equivocal by IHC than by FISH. Occasional cases (2 in
S71
this cohort: < 1%) show absolute discordance between IHC and FISH. If IHC ‘triage’ had been employed (only equivocal or þ ve cases reflexed to FISH), one of 34 FISH þ ve cases (3%) would have been missed.
OROPHARYNGEAL SQUAMOUS CELL CARCINOMA (OPSCC), A PRACTICAL PROGNOSTIC IMMUNOPHENOTYPIC PANEL C. S. Ng, W. H. Lam, Paul K. S. Chan, S. T. H. Lo and WK Chong Caritas Medical Center, Yan Chai Hospital and the Chinese University of Hong Kong, Hong Kong Aims: Human papillomavirus (HPV)-positive OPSCC accounts for 25% of OPSCC. HPV E6 and E7 proteins inactivate the retinoblastoma gene causing overexpression of the p16 protein, which is regarded as HPV surrogate. There is evidence that p16 expression is an independent prognostic factor and cyclin D1 overexpression associated with poor prognosis in OPSCC. HPVþ OPSCC carries better prognosis than HPV – OPSCC, and is characterised by histological poor squamous differentiation (PD) and advanced regional nodal metastasis. This study aimed to study correlation among the morphology, immunophenotype and HPV DNA in OPSCC. Methods: The morphology, immunophenotype and HPV DNA in OPSCC of 147 patients in Hong Kong were studied, using an immunoautostainer (p16 and cyclin D1), polymerase chain reaction and typing by sequencing for HPV DNA detection. Results: Twenty-seven (18%) tumours carried HPV16 DNA, 56 (38%) were p16þ and 105 (72%) cyclin D1þ. Fifty-two (35%) were PD tumours. Strong statistical correlation ( p < 0.001) was demonstrated between HPV16 DNAþ and p16þ; p16þ and PD; cyclin D1þ and p16 – and HPV16 DNA – . Twenty-nine p16þ cases did not contain HPV16 DNA, showing p16 is not a perfect HPV surrogate. Discussion: This study showed that p16 is strongly correlated with the good prognostic feature PD, while cyclin D1 is correlated with the poor prognostic features p16 – and HPV DNA – . We conclude a simple immunophenotypic panel of p16 and cyclin D1 is a practical approach for prognostication of HPVþ OPSCC.
PAPILLARY CARCINOMA IN STRUMA OVARII: A CASE REPORT Ann Niap, Swapna Sengupta, Denys Fortune and Ross Stillwell Dorevitch Pathology, Ballarat Base Hospital, Vic, Australia Introduction: Struma ovarii is a form of teratoma composed predominantly of thyroid tissue, comprising 2.7% of all ovarian teratomas.1 Malignancy may occur in 5–10% of struma ovarii.2 There is controversy as to the best management and follow-up of these cases. We describe a rare case of a 45-year-old woman with struma ovarii showing features of papillary carcinoma. Case report: The patient presented with 12 months of pelvic pain and heavy irregular vaginal bleeding. A pelvic ultrasound showed a small left-sided dermoid cyst. Laparoscopic salpingo-oophorectomy was performed. Sections of the ovarian cyst showed a mature teratoma. Thyroid tissue comprised approximately 50% of the specimen. The follicular cells displayed nuclear features of papillary carcinoma. This
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
COLORECTAL ADENOCARCINOMA WITH THE SERRATED NEOPLASIA PATHWAY Renn Montgomery and Tao Yang Department of Anatomical Pathology, Liverpool Hospital, Liverpool, NSW, Australia The conventional pathway for the development of colorectal carcinoma (CRC) has been well described, and involves mutations in the APC gene, as well as alterations in p53 and the development of microsatellite instability. A more recently described pathway implicates sessile serrated lesions in the development of colorectal carcinoma, illustrated by a case we report of a 66-year-old male presenting with three synchronous adenocarcinomas, with multiple sessile serrated adenomas (SSAs). BRAF V600E mutation was detected and there was sporadic microsatellite instability. The serrated neoplasia pathway differs from the conventional pathway, involving mutations in the BRAF oncogene, as well as epigenetic mechanisms leading to abnormal hypermethylation of tumour suppressor genes. This methylation may involve MLH1, leading to sporadic microsatellite instability, as seen in our case. Sessile serrated lesions are the precursor for this pathway, and it is possible that they may progress to carcinoma more rapidly than conventional adenomas. They are often difficult to identify and completely remove. Thus, screening of SSAs and identification of SSA polyposis to prevent CRC may be of particular clinical significance.
THE COMBINATION OF FISH AND IHC FOR ALK ASSESSMENT IN NSCLC IS MORE POWERFUL THAN EITHER TECHNIQUE ALONE A. L. Morey, B. Brown, D. Riley, G. Gracie and M. R. Qiu Department of Tissue Pathology and Cancer Genetics, SydPath, St Vincent’s Hospital, Darlinghurst, Sydney, NSW, Australia Aim: Examination of the proposition that detection of ALK overexpression by IHC in NSCLC may act as triage or replacement for FISH. Method: Results on 221 NSCLCs referred for ALK FISH testing (Abbott-Vysis LSI ALK Breakapart FISH Probe) were reviewed, FISH hybridisation pattern classified and compared to ALK IHC (Clone D5F3). Results: 10 cases (4.5%) had insufficient material for testing. Thirty-four cases were FISH þ ve, four equivocal (1.8%) and 173 negative. Seventeen positive cases had classic ‘split’ signal; 14 had isolated 3’ red signals, two had combined pattern and two cases (both IHC þ ve) had variant patterns with additional 5’ (green) signals (previously regarded as FISH–ve). Twenty-nine of these 34 cases were IHC þ ve (85% IHC sensitivity), three were IHC equivocal, 1 was untested, and 1 IHC–ve. Two FISH equivocal cases (minimal split) were strongly IHC þ ve. One of 173 FISH–ve cases was strongly IHC þ ve. IHC on 196 cases scored 32 as positive, 14 equivocal (7%) and 150 negative. 25 IHC þ ve cases were straightforward FISH þ ve, six had variant/equivocal FISH patterns, one was FISH–ve (97% IHC specificity). Three of 14 IHC equivocal cases were FISH þ ve, as was one IHC–ve case. Discussion: Combination of IHC and FISH for detection of ALK mutation is more powerful than either test in isolation. Without availability of IHC, six cases with equivocal or variant FISH patterns would likely have been missed, however four times more cases are equivocal by IHC than by FISH. Occasional cases (2 in
S71
this cohort: < 1%) show absolute discordance between IHC and FISH. If IHC ‘triage’ had been employed (only equivocal or þ ve cases reflexed to FISH), one of 34 FISH þ ve cases (3%) would have been missed.
OROPHARYNGEAL SQUAMOUS CELL CARCINOMA (OPSCC), A PRACTICAL PROGNOSTIC IMMUNOPHENOTYPIC PANEL C. S. Ng, W. H. Lam, Paul K. S. Chan, S. T. H. Lo and WK Chong Caritas Medical Center, Yan Chai Hospital and the Chinese University of Hong Kong, Hong Kong Aims: Human papillomavirus (HPV)-positive OPSCC accounts for 25% of OPSCC. HPV E6 and E7 proteins inactivate the retinoblastoma gene causing overexpression of the p16 protein, which is regarded as HPV surrogate. There is evidence that p16 expression is an independent prognostic factor and cyclin D1 overexpression associated with poor prognosis in OPSCC. HPVþ OPSCC carries better prognosis than HPV – OPSCC, and is characterised by histological poor squamous differentiation (PD) and advanced regional nodal metastasis. This study aimed to study correlation among the morphology, immunophenotype and HPV DNA in OPSCC. Methods: The morphology, immunophenotype and HPV DNA in OPSCC of 147 patients in Hong Kong were studied, using an immunoautostainer (p16 and cyclin D1), polymerase chain reaction and typing by sequencing for HPV DNA detection. Results: Twenty-seven (18%) tumours carried HPV16 DNA, 56 (38%) were p16þ and 105 (72%) cyclin D1þ. Fifty-two (35%) were PD tumours. Strong statistical correlation ( p < 0.001) was demonstrated between HPV16 DNAþ and p16þ; p16þ and PD; cyclin D1þ and p16 – and HPV16 DNA – . Twenty-nine p16þ cases did not contain HPV16 DNA, showing p16 is not a perfect HPV surrogate. Discussion: This study showed that p16 is strongly correlated with the good prognostic feature PD, while cyclin D1 is correlated with the poor prognostic features p16 – and HPV DNA – . We conclude a simple immunophenotypic panel of p16 and cyclin D1 is a practical approach for prognostication of HPVþ OPSCC.
PAPILLARY CARCINOMA IN STRUMA OVARII: A CASE REPORT Ann Niap, Swapna Sengupta, Denys Fortune and Ross Stillwell Dorevitch Pathology, Ballarat Base Hospital, Vic, Australia Introduction: Struma ovarii is a form of teratoma composed predominantly of thyroid tissue, comprising 2.7% of all ovarian teratomas.1 Malignancy may occur in 5–10% of struma ovarii.2 There is controversy as to the best management and follow-up of these cases. We describe a rare case of a 45-year-old woman with struma ovarii showing features of papillary carcinoma. Case report: The patient presented with 12 months of pelvic pain and heavy irregular vaginal bleeding. A pelvic ultrasound showed a small left-sided dermoid cyst. Laparoscopic salpingo-oophorectomy was performed. Sections of the ovarian cyst showed a mature teratoma. Thyroid tissue comprised approximately 50% of the specimen. The follicular cells displayed nuclear features of papillary carcinoma. This
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.