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Idiopathic granulomatous mastitis (IGM) is a benign mimic of breast carcinomas. It is defined histologically by the presence of granulomas and inflammation. The closely related cystic neutrophilic granulomatous mastitis (CNGM) shows lipogranulomas, with a reported association with corynebacteria. A large cohort of IGM was reviewed to compare clinical, microbiological and histological features between non-CNGM IGM and CNGM. Cases of IGM were reviewed for histological parameters including the presence of lipogranulomas and composition of inflammatory cells. Clinical data were obtained through hospital records. The cohort included 79 cases, including 51 non-CNGM IGM and 28 CNGM. Comparing non-CNGM IGM and CNGM, there were no differences in clinical or demographical data, other than a younger age of presentation (36.2 vs 41.5 years, p=0.012) for CNGM. Most IGM resolved within the follow-up period (n=57/64, 89.1%), with similar outcomes regardless of treatment (p0.05). In CNGM, there were more infiltrates of neutrophils (p=0.001), histiocytes (p=0.047), and multinucleated giant cells (p=0.006), but less lymphocytes (p=0.008). Corynebacteria was cultured in two (25%) cases of CNGM, and one non-CNGM IGM (14.3%). Gram-positive bacilli were identified in two cases of CNGM. 'Early' lipogranulomas were observed closely associated to inflamed ducts in three cases of CNGM. Apart from age, there was no distinct clinical or microbiological feature for CNGM. These findings do not support CNGM as a distinct entity. Rather, CNGM-pattern may represent a continuum of IGM, possibly age-related and attributable to ductal inflammation and cystic changes in the breast parenchyma.

Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon sarcoma with a deceptively bland-looking morphology that disguises its malignant clinical behavior. It shows distinctive chromosomal translocations resulting in fusion of FUS with the CREB3L2 gene in most cases and CREB3L1 in rare cases. Thus molecular studies are particularly helpful in the diagnosis of this bland-looking sarcoma. We report 2 cases of LGFMS serendipitously found to harbor a novel alternative EWSR1-CREB3L1 gene fusion, as confirmed by DNA sequencing of reverse transcriptase-polymerase chain reaction products and fluorescence in situ hybridization. One patient was a child who presented with a subcutaneous nodule on the lower leg, and the other was a middle-aged woman who had a mass lesion over the proximal thigh. Morphologically, one case showed a spindle cell tumor with hyalinization and giant rosettes, whereas the other showed classical histology of LGFMS with focal metaplastic bone formation. Immunostaining for MUC4 showed extensive positive staining. Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma.

Tsang A K H, Chan S K, Lam C C F, Lui P C W, Chau H H L, Tan P H & Tse G M (2011) Histopathology 59, 600–608 Phyllodes tumours of the breast–differentiating features in core needle biopsy Aims: To investigate the usefulness of histological features in the differentiation of fibroepithelial lesions of the breast (phyllodes tumours and fibroadenomas) in core needle biopsies. Methods and results: Forty-nine and 69 excision-proven core biopsies of phyllodes tumours and fibroadenomas, respectively, were evaluated histologically for stromal cellular changes (overall stromal cellularity, variability in stromal cellularity, stromal cell pleomorphism, and mitotic count) and stromal architectural changes (stromal overgrowth, fragmentation of the cores, and fat in stroma). In core needle biopsies of phyllodes tumours, overall stromal cellularity, stromal cell pleomorphism and mitotic count showed good correlation with excisions. In phyllodes tumours, core needle biopsy diagnosis showed increased certainty with increasing degree of malignancy. Core biopsies of phyllodes tumours showed more consistent stromal cellular changes (overall stromal cellularity, variability in stromal cellularity, stromal pleomorphism, and mitotic count) than those of fibroadenomas. These parameters were also useful for differentiation between benign and malignant fibroepithelial lesions. For grading phyllodes tumours, stromal cell pleomorphism and mitotic activity were found to be helpful. Conclusions: In the core biopsy assessment of phyllodes tumours, evaluation of selected histological parameters, particularly those pertaining to stromal cellular changes, is helpful.

AIMS Mammary metaplastic carcinoma is a rare breast carcinoma, and may present diagnostic difficulty. Alpha-B-crystallin has been recently reported to be expressed in basal-like and metaplastic carcinomas. METHODS AND RESULTS Thirty-three metaplastic carcinomas, 44 conventional high-grade carcinomas and 28 mesenchymal spindle cell neoplasms as controls were assessed for their expression of αB-crystallin and conventional basal-like phenotypic markers CK5/6, CK14, p63, c-kit and epidermal growth factor receptor (EGFR) by immunohistochemistry. Alpha-B-crystallin staining was positive in 68% of the metaplastic carcinomas with cytoplasmic staining in all tumour cell components. CK5/6, CK14, p63, c-kit and EGFR stained 43%, 68%, 45%, 21% and 25% of the metaplastic carcinomas, respectively. Combining these markers, 84% of the metaplastic carcinomas expressed either αB-crystallin or CK14. In comparison, only 14% (six cases) of conventional high-grade carcinoma and 7% (two cases) of mesenchymal spindle cell neoplasm expressed αB-crystallin; all but one of these carcinomas were ER/PR/HER2 triple-negative. CONCLUSIONS Using αB-crystallin for diagnosis of metaplastic carcinoma gives a 68% sensitivity, 88% specificity, 74% positive predictive value, 85% negative predictive value and 78% accuracy. The sensitivity is enhanced to 84% with combinations of αB-crystallin/CK14. Alpha-B-crystallin may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.

This study evaluated the expression of biological markers of breast cancers with brain metastases. Eighteen paired tumors were assessed, with 42 non-brain-metastasizing breast cancers that were stained with ER, PR, HER2, CK5/6, p63, and Ki67, and were also classified into intrinsic subtypes. The expression patterns between the breast tumors with brain metastases were compared to the brain metastases and the controls. Breast cancers with brain metastases were of higher grade and showed higher incidence of lymph node metastases at initial diagnosis and higher EGFR, p63, and Ki67 expression. In the group of breast cancers with brain metastases, the brain metastases showed higher HER2, CK5/6, and Ki67 expression compared to the breast primaries. There was also a higher incidence of basal subtype and a lower incidence of luminal subtype. When tumors metastasized, changes in hormonal receptor (22%) and HER2 (6%) status were observed. We concluded that breast cancers with higher grade, lymph node involvement at diagnosis, high EGFR, p63, and Ki67 expression, and of basal subtype were at higher risk for brain metastases, and that both hormonal receptors and HER2 status may change in brain metastases.

Jara-Lazaro A R, Akhilesh M, Thike A A, Lui P C-W, Tse G M-K & Tan P H (2010) Histopathology 57, 220–232 Predictors of phyllodes tumours on core biopsy specimens of fibroepithelial neoplasms Aims: To establish histological and biological parameters that can predict phyllodes tumours on core biopsy specimens of indeterminate fibroepithelial neoplasms. Methods and results: Core biopsy specimens of fibroepithelial lesions diagnosed at the Department of Pathology, Singapore General Hospital from 2002 to 2007 were reviewed. Cases in which phyllodes tumour was favoured, or could not be ruled out, were evaluated for stromal cellularity/distribution, nuclear atypia and mitoses, stromal overgrowth, epithelial fronding, epithelial hyperplasia, configuration of lesional edge, presence of pseudoangiomatous stromal hyperplasia and of adipose tissue. Antibodies to Ki67, topoisomerase IIα, CD34, CD117 and Bcl-2 were applied to sections subjected to immunohistochemistry using the streptavidin–biotin method. Findings were correlated with subsequent excisions. Of 261 core biopsy specimens of fibroepithelial lesions, 98 (37%) comprised cases in which phyllodes tumour could not be excluded and 57 (58%) had subsequent open surgical excisions. Marked stromal hypercellularity (5/5; 100%) and nuclear atypia (1/1; 100%), stromal overgrowth (17/17; 100%), mitoses ≥2/10 high-power fields (18/18; 100%) and ill-defined lesional borders (16/16 phyllodes tumours; 100%) were features in core biopsy specimens that exclusively predicted phyllodes tumour on excision. Moderate stromal hypercellularity (20/27 phyllodes tumours; 74%), stromal overgrowth, moderate nuclear atypia (14/16 phyllodes tumours; 87%), pseudoangiomatous stromal hyperplasia (19/23 phyllodes tumours; 83%) significantly correlated with their subsequent excisions. Immunohistochemical markers Ki67 ≥5% and topoisomerase IIα≥5%, and reduced or patchy CD34 on core biopsy specimens correlated significantly with a diagnosis of phyllodes. Conclusions: Stromal hypercellularity, combined with key histological features and immunohistochemical markers Ki67, topoisomerase IIα and CD34, reinforced by clinical findings, can predict phyllodes tumours on core biopsy specimens.

Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers in the management of breast carcinoma. They are not always analyzed in distant metastatic and locally recurrent breast cancers. We compared immunohistochemical expression in a series of primary breast carcinomas with their distant metastases (n = 72) and local recurrences (n = 45) and analyzed the impact of any changes on survival. Discordance rates between primary and metastatic and between primary and locally recurrent lesions, respectively, were 18% (13/72) and 13% (6/45) for ER, 42% (30/72) and 33% (15/45) for PR, and 7% (5/72) and 2% (1/45) for c-ERBB2. There was statistically significant discordance between primary and metastatic PR status (P = .017; κ = 0.201). Among locally recurrent tumors, 15 (33%) of 45 revealed discordance for PR (P = .006; κ = 0.366). We observed a trend for shorter survival among women with ER– metastatic and locally recurrent tumors regardless of the primary tumor ER status. Our findings suggest a benefit for routine evaluation of ER, PR, and c-ERBB2 status in distant metastatic and locally recurrent breast cancer for therapeutic and prognostic purposes. Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers in the management of breast carcinoma. About 60% to 70% of breast carcinomas express ER protein, and these tumors are associated with better prognosis. 1 Detecting ER expression in a tumor depends on physiologic and technical factors, including menopausal status, endocrine therapy, tumor sampling and intratumoral heterogeneity, tissue fixation, method of examination (biochemical, immunohistochemical), and type of antibody used. 2-4

Tse G M, Tan P-H, Lacambra M D, Jara-Lazaro A R, Chan S-K, Lui P C, Ma T K F, Vong J S, Ng D C H, Shi H-J & Lam W W (2010) Histopathology56, 481–488 Papillary lesions of the breast—accuracy of core biopsy Aims: To assess the accuracy of diagnosing papillary breast lesions in core needle biopsy. Methods and results: One hundred biopsy specimens of papillary breast lesions were reviewed and compared with the final excisional diagnoses. The discordant biopsy specimens were stained for oestrogen receptor (ER), cytokeratin (CK) 14 and p63, and these specimens were reclassified based on these results. The overall core biopsy accuracy, false-positive and false-negative rate were 79%, 5% and 16%, respectively. A benign core biopsy specimen diagnosis gave a false-negative rate of 10%, and malignant core biopsy specimen diagnosis did not give any false-positive results. Using homogeneous ER (epithelial), positive CK14 (epithelial) and p63 (myoepithelial) immunoreactivity as benign criteria, the discordant rate was reduced by 30% and 69% when using all three or two of these three criteria for diagnosis. However, false-positive and -negative cases could not be totally eliminated. Conclusions: Immunohistochemistry is helpful in core biopsy diagnosis of papillary breast lesions, but some cases remained misdiagnosed.

Inflammatory pseudotumor is a disease with unsettled pathogenesis. The brain is a rare site of occurrence. The aim of this study is to investigate ALK-1 protein expression and IgG4-positive plasma cells detection in 4 intracranial inflammatory pseudotumors. Three dural-based and 1 intraventricular inflammatory pseudotumors were retrieved from the hospitals' archive. The data on clinical presentation, radiological findings, procedure undertaken, and patients' progress were collected. Sections from the excised lesions were examined under hematoxylin and eosin, histochemical, and immunohistochemical staining including ALK-1 and IgG4. All 4 cases displayed typical histological features of inflammatory pseudotumor with dense lymphoplasmacytic infiltrate admixed with small number of benign-looking spindle cells in a collagenous stroma. Three cases exhibited high density of IgG4-positive plasma cells per high-power field. ALK-1 was negative. ALK expression was not found in any of our cases. On the contrary, the detection of significant number of IgG4-positive plasma cells in 3 inflammatory pseudotumors suggests that a considerable proportion of intracranial inflammatory pseudotumor may belong to the IgG4-related subgroup. Hence, a trial of corticosteroid after histological confirmation may be valid to avoid unnecessary risk-taking neurosurgical procedures or in cases with incomplete tumor removal.

Myopericytoma is an uncommon, benign perivascular myoid cell tumor that occurs almost exclusively in somatic soft tissues. We report 2 cases occurring in patients with acquired immunodeficiency syndrome who show unusual clinical and biologic features. One patient presented with a bronchial mass and the other developed mass lesions of the tongue, vocal cord, and brain. Histologically, oval to plump spindly tumor cells with uniform nuclei and scanty cytoplasm formed sheets or cuffs around gaping or narrow vascular spaces. Focally, these areas merged into fascicles of more elongated cells with eosinophilic cytoplasm. The tumor cells were immunoreactive for actin but not desmin, and showed uniform labeling for Epstein-Barr virus (EBV) encoded RNAs on in-situ hybridization. Both patients were alive 5 years after incomplete excision of the lesions. In conjunction with another case reported in the literature, myopericytoma occurring in acquired immunodeficiency syndrome patients exhibits several features distinct from sporadic myopericytoma: presentation in anatomic sites other than somatic soft tissues, frequent presence of multifocal disease, and association with EBV. This tumor type therefore also broadens the spectrum of neoplasms associated with EBV.

Previous studies have suggested that breast cancer in young women has more aggressive biological features and poorer prognosis. However, the role of biological markers in these patients is not well understood. We aimed to learn more about this disease in a cohort of 125 young women from Singapore, Japan and Hong Kong, aged 35 years or less, with invasive breast cancer by evaluating the expression of vimentin and the basal cytokeratins CK14, CK5/6 and 34 beta E12. Both standard paraffin sections and tissue microarrays were used in the immunohistochemical evaluation of expression patterns of these four biological markers. CK5/6, CK14, vimentin and 34 beta E12, in increasing order of proportion, were detected in invasive carcinomas. Basal cytokeratins and vimentin showed significant inverse relationship with estrogen and progesterone receptor status while CK14 expression was found to be directly associated with c-erbB2 status. Basal cytokeratins and vimentin immunoreactivities were directly associated with CD117 and EGFR expression. Vimentin and 34 beta E12 immunopositivity correlated with tumor size, while vimentin was associated with higher histological grade. Our findings are in concert with reports that expression of basal cytokeratins and vimentin is correlated with adverse pathological parameters.

Summary Aims Elderly breast cancers are associated with a more favourable biological marker profile and higher proportion of specific subtypes, some of which are of low histological grade. We reviewed the fine needle aspiration cytology (FNAC) to assess the cytological characteristics and any clues to assist in the diagnosis. Methods The aspirates of 140 cancers of various histological types and grades and 39 benign lesions were evaluated for 13 cytological parameters including cellularity of the direct and cytospin smears, epithelial cell clusters, cellular atypism, cytoplasmic features, vacuoles, mitotic figures, presence of myoepithelial cells, single background epithelial cells, the presence of naked nuclei, stromal fragments and necrosis. Results We found that the presence of background single epithelial cells, atypism of such cells, absence of benign appearing epithelial fragments, nuclear atypism of the epithelial cells within the fragments, presence of moderate amount of cytoplasm of these cells, absence of myoepithelial cells within the cluster, and absence of bipolar nuclei in the background have a strong association with malignancy. Scoring only the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei in a scoring system can differentiate between benign and malignant aspirates with high (>90%) sensitivity and specificity. Conclusions Assessing the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei facilitates identification of malignancy in the aspiration of breast lesions from elderly patients.

Aim: Cytological diagnosis of mammary papillary lesions is difficult. We reviewed the previous cytology diagnosis of 23 papillomas and 11 papillary carcinomas and specific cytological features that may assist in differentiating these entities. Methods: The cytology preparations were reviewed for (i) overall cellularity; (ii) epithelial cell ball devoid of fibrovascular cores; (iii) single cells; (iv) papillary fragments and their morphology. Results: The overall diagnostic accuracy was 59%, atypical rate was 24%, and the error (combined false positive and negative) rate was 17%. For overall cellularity, six, 14 and three cases of papillomas and six, three and two cases of papillary carcinoma showed low, moderate to high cellularity respectively. Cell balls were present in mild to moderate number in 20 papillomas and ten papillary carcinomas. The background single cells were absent, present in low or moderate to high numbers in seven, ten and six papillomas and three, three and five papillary carcinomas respectively. Papillary fragments were absent, present in small, moderate or large quantities in nine, four, eight and two papillomas and six, three, one and one papillary carcinomas respectively. There is no demonstrable quantitative difference between papilloma and papillary carcinoma for all these parameters. Qualitatively, the cell balls and single cells showed higher degree of atypia in papillary carcinoma, and the papillary fragments were more elaborate and slender. Summary: Cytological diagnosis of papillary lesions shows significant error rate with overlapping features. Cellular atypia and fragments with long and slender papillae with ramifying edges favours papillary carcinoma.

Summary Aim To determine the pathognomonic diagnostic cytological features of invasive micropapillary carcinoma of the breast which is a poor prognostic subtype of infiltrating ductal carcinoma. Methods A series of 20 histologically proven tumours were reviewed retrospectively to evaluate the various cytological features, including tumour morules, isolated malignant cells, staghorn epithelial structures, mucinous background and apocrine metaplasia. Results Tumour morules formation and isolated malignant cells were the two most reliable and constant cytological features, being present in 75% (15/20 cases) of cases. Staghorn epithelial structures were present in 35% (7 cases). Mucinous background (2 cases, 10%) and apocrine metaplasia (4 cases, 20%) of the tumour cells were seen in a few cases only and did not appear very helpful. Conclusion Tumour morules formation, isolated malignant cells and staghorn epithelial structures are the most reliable cytological features, and the presence of these should raise suspicion of invasive micropapillary carcinoma.

Sir,Primary hepatic carcinoid tumour (PHCT) is an exceedingly rare tumour. We report two cases of PHCT. Both patients had similar symptoms, clinical and imaging findings, and very favourable outcom...

Summary Aims p63 has been recently reported to be expressed in sarcomatoid/metaplastic carcinoma of the breast, in addition to its role as a myoepithelial marker. A large series of 34 metaplastic carcinomas, including cases with pure epithelial component (squamous cell and adenosquamous carcinomas), biphasic tumours with carcinomatous and sarcomatoid components and monophasic tumours with only spindle cell component, were evaluated for p63 expression with respect to the different cellular components. Methods All of the metaplastic carcinomas were assessed for p63 and conventional epithelial and mesenchymal markers of AE1/3, CAM5.2 and vimentin by immunohisto-chemistry. Results All of the different categories of metaplastic carcinomas showed similar clinico-pathological features (patient age, tumour size, nuclear grade, mitotic activity, lymph node status and hormonal receptor status). For metaplastic carcinoma with epithelial component only, p63 was only expressed in the squamous cell component, but not the adenocarcinoma component. Eight of the 10 tumours were positive for p63. For the tumours with sarcomatoid component, either singly or together with carcinomatous component, p63 was positive in 14 of 24 cases. Pure sarcomas and carcinomas were all negative for p63 staining by immunohistochemistry, thus rendering p63 staining highly specific for diagnosing metaplastic carcinoma. Conclusions Using p63 for diagnosis of metaplastic carcinoma gives a sensitivity of 65%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 66% and an accuracy of 78%. p63 may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.

Phyllodes tumors are fibroepithelial neoplasms typified by stromal proliferation. We have previously shown the role of pathologic parameters and the prognostic significance of p53 and CD117 protein expression in these tumors. In this study, we evaluated the expression of heparan sulfate, which has been implicated in many biological processes such as cell adhesion, embryogenesis, and tumorigenesis (including malignant transformation of mammary cells) in 232 breast phyllodes tumors. We used a monoclonal antibody, 10E4, to examine the localization of heparan sulfate in phyllodes tumors by immunohistochemistry. The immunoreactivity of both epithelial and stromal components was examined and analyzed with pathological parameters and other immunohistochemical markers, including p53, MIB1, bcl2, and CD117. Stromal 10E4 expression was significantly associated with tumor grade, stromal p53, and MIB1 expression in proliferating cells, suggesting that heparan sulfate may participate in malignant tumor growth.

In May 1996, a 56-year-old man in Hong Kong presented with fever and dry cough and had miliary shadows in bilateral lung fields on chest radiographs. The patient had migrated from Shanghai more than 10 years previously and worked as a cook. Upon admission, he was also found to have diabetes with poor glycaemic control. The clinical diagnosis was miliary tuberculosis (TB), however, all mycobacterial cultures were negative. The man was put on empirical anti-tuberculosis medication. Thrombocytopenia developed shortly afterwards. Bone marrow biopsy revealed foci of epithelioid cell granuloma and normal haematopoiesis, consistent with tuberculosis. Four months later, he presented with persistent bilateral epididymal masses with scrotal pain for 2 weeks. Tender and hardened epididymes were found upon physical examination. The clinical diagnosis was TB epididymitis. Mycobacterial culture of his early morning urine was negative. The empirical anti-TB treatment was lengthened to a total of 18 months until November 1997. In 1998, an incidental finding of bilateral adrenal masses was noted upon computed tomography (CT) of his abdomen. These masses were of soft tissue consistency density with no contrast enhancement in early and delayed phases. CT-guided fine needle aspiration of the right adrenal mass revealed necrotic tissue only in two successive examinations. Ziehl–Neelsen (ZN) stain was negative. Follow-up CT scans indicated no significant interval change in the size of the masses. In 2002, the man complained of insidious onset of left shoulder pain and swelling, as well as knee pain. Magnetic resonance imaging (MRI) and arthroscopy of the left shoulder were performed. MRI revealed rice bodies distending the joint capsule, especially over the subcoracoid and subdeltoid bursae. The clinical diagnosis was TB arthritis and osteomyelitis. Histology of the synovectomy specimen showed oedematous tissue with moderate chronic inflammation and a small focus of granulomatous inflammation. Neither caseous necrosis nor multinucleated giant cell was noted. ZN stain was again negative. The bacterial and mycobacterial cultures of the left shoulder synovial tissue and left knee aspirate were negative. No anti-TB treatment was prescribed. In January 2004, the man presented with significant weight loss. Workup revealed elevated alpha-fetoprotein. A liver tumour was detected, measuring 60640630 mm in greatest dimension and occupying the right lobe of liver, associated with unresolved bilateral adrenal enlargement. A short Synacthen test confirmed normal hypothalamic-pituitary-adrenal function. Partial hepatectomy (central), right adrenalectomy and cholescystectomy were performed. The right adrenal gland measured 55635618 mm in size and weighed 15 g. Serial sectioning showed a nodule with necrotic yellowish material (Fig. 1). Figures 2A and B show the H&E and Grocott stains of the sections of the adrenal lesion, respectively.

Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours.To investigate NOS expression in phyllodes tumours of varying degrees of malignancy.One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed.Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours.Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

A retrospective review of 185 mammary phyllodes tumors (105 benign, 51 borderline, 29 malignant) from 4 centers was performed by immunohistochemistry to investigate the expression of vascular endothelial growth factor in the epithelial and stromal cells of mammary phyllodes tumors. The correlation of vascular endothelial growth factor with tumor grade, stromal cell nuclear pleomorphism, cellularity, mitotic rate, margin histomorphology, and the stromal microvessel density was evaluated. Vascular endothelial growth factor expression was found in the epithelium in 29% and in the stromal cells in 31% of cases. There was significant increase of vascular endothelial growth factor expression in the stromal cells with increasing degree of malignancy, but not the epithelium. Microvessel density in the stroma also showed significant correlation with tumor malignancy, and a correlation was shown with the stromal vascular endothelial growth factor expression. Statistical overlap of stromal vascular endothelial growth factor and microvessel density in predicting malignancy suggests that angiogenesis may be an effector mechanism for vascular endothelial growth factor. Assessment of stromal VEGF may be useful as an adjunctive diagnostic criterion in the histologic assessment of malignancy in phyllodes tumors.

Sir,We describe herein a case of metastatic Merkel cell carcinoma (MCC) in a post‐renal transplant patient. The incidence and clinical course of MCC in renal transplant recipients appears different...

Sir,Astroblastoma is a rare and controversial brain tumour of uncertain histogenesis. The tanycyte has been suggested as a possible cell origin. The tumour usually affects children and young adults...

(2005). Myiasis by Chrysomya bezziana in surgical pathology. Pathology: Vol. 37, No. 1, pp. 80-82.

Minichromosome maintenance (MCM) proteins 2-7 are important in DNA replication licensing. Functional roles beyond licensing are speculated. In addition, significances in medulloblastoma (MB) remain unclear. In this study, we showed the frequent deregulation of MCM2 and MCM3 expression in 7 MB cell lines and 31 clinical samples. Moreover, DAOY and ONS76 and the clinical samples expressed elevated MCM7 transcripts with genomic gain of the gene. Immunopositivity restricted to tumor cells was found in 41, 37 and 53 out of 73 MB cases for MCM2, MCM3 and MCM7, respectively. High-MCM3 expression was associated with poor prognosis. Knockdowns of these MCMs significantly inhibited anchorage-dependent and -independent MB cell growth. The inhibition of MCM3 expression by small interfering RNA knockdown was related to G1 arrest with reduced cyclin A expression, whereas the MCM2- and MCM7-knocked-down cells arrested at G2/M with increased cyclin A expression. Interestingly, we demonstrated the links of these MCMs with cell migration and invasion using wound-healing and Transwell migration/invasion assays. Exogenous overexpression of MCM2, MCM3 and MCM7 increased anchorage-independent cell growth, and also cell migration and invasion capabilities in MB cells. The knockdown reduced the number of filopodial cells and the cells with intense stress fibers by blocking cdc42 and Rho activation. Taken together, deregulation of MCM2, MCM3 and MCM7 expression might be involved in MB tumorigenesis and we revealed undefined roles of these MCMs in control of MB cell migration and invasion.

The blood–brain barrier (BBB) hinders drug delivery to the brain parenchyma. The ultimate goal of brain drug targeting technology is to deliver therapeutics across the BBB with a diverse collection of molecular transport systems. Receptor-mediated transcytosis (RMT) is one such class of transport system. Insulin and transferrin, as well as other endogenous peptides, employ the vesicular trafficking machinery of the endothelium to transport substances between the blood and the brain. In addition to vector development, strategies for coupling drugs to the vector that give high-efficiency coupling are the other important element for RMT. After the BBB-targeting vector–therapeutic conjugates have crossed the BBB, there may still be a need to target them to a specific population of cells in the brain. This review will focus on two major aspects of RMT brain drug delivery: new advances of existing RMT systems and development of new BBB transport vectors and specific RMT targets.

A significant proportion of ductal carcinomas in situ (DCISs) of the breast diagnosed on core biopsies had invasion upon excision. An assessment of various invasion predictors in the biopsies yielded conflicting results. A cohort of 157 cases with needle core biopsy diagnosed with DCISs (including 109 histologically proven DCISs, and 48 cases with invasion upon excision) were evaluated for the numbers of positive and total cores, the percentage of positivity, lobular cancerization, tumor nuclear grade, necrosis, calcification, predominate histological pattern, lymphocytic infiltrate and excisional tumor size. The mean positive core percentage and excisional tumor size were 76% and 2.8 cm for invasive and 66% and 1.9 cm for noninvasive groups. In the biopsy of the invasive group, cancerization of lobules was present in 52%, and nuclear grades 1, 2 and 3 were present in 31, 31 and 38%, respectively. Large comedo and small noncomedo necroses were present in 48 and 10%, whereas large and small calcifications were present in 16 and 21%. Solid, cribriform and papillary patterns were observed in 88, 38 and 21%, respectively. Moderate to marked lymphoid infiltrate was present in 31%. In the biopsy of the noninvasive group, cancerization of lobules was present in 69%, and the nuclear grades 1, 2 and 3 were present in 23, 48 and 29%, respectively. Large comedo and small noncomedo necroses were present in 35 and 11%, whereas large and small calcifications were present in 33 and 23%. Solid, cribriform and papillary patterns were observed in 85, 39 and 9%, respectively. Moderate to marked lymphoid infiltrate was present in 36%. Comparing these groups, a higher positive core percentage, papillary pattern and less cancerization of lobules in the cores and larger excisional tumor size were associated with a higher chance of invasion. Calcification, necrosis and nuclear grade were not significant invasion predictors.

Blood–brain barrier (BBB) limits drug delivery to the brain parenchyma. The ultimate goal of brain drug targeting technology is to deliver therapeutic agents across BBB. Insulin or transferrin as well as other endogenous peptides undergo receptor-mediated transcytosis or transport (RMT) across the BBB in vivo. Certain peptidomimetic monoclonal antibodies (mAb) for insulin receptor or transferrin receptor can also cross the BBB via RMT on the endogenous receptors. These mAb can act as molecular Trojan horses to shuttle into the brain a wide range of therapeutics including recombinant proteins, antibodies, RNA interference drugs, or non-viral gene products. During the last two decades, RMT-based brain drug transport techniques have been developed. This chapter will focus on introducing three major technologies in the arena of RMT brain drug delivery: (1) Avidin–biotin technology; (2) Fusion protein technology; and (3) Trojan horse liposomes (THLs).

Rhabdoid tumor cells are typically observed in atypical teratoid/rhabdoid tumor (AT/RT) but may also be seen in meningioma,glioma, melanoma, rhabdomyosarcoma and metastatic carcinoma.We present an astroblastoma with unusual rhabdoid features which is rarely described in the English literature. Apart from the rhabdoid tumor cells, all the histopathological features typical for astroblastoma are present in this case. These features include pseudopapillary arrangement, astroblastic pseudorosettes, perivascular hyalinization and calcifications, absence of fibrillary background and a pushing tumor border. The tumor cells display a multilineage immunohistochemical profile. In addition, diffuse and strong membranous and cytoplasmic dot-like pattern is appreciated with epithelial membrane antigen (EMA). The diagnosis of astroblastoma is also well supported by the age of presentation, anatomical location and radiological features of the tumor.We believe that on top of the above-mentioned unusual tumors with rhabdoid cells, astroblastoma should also be considered in the list of differential diagnosis.

Objective We conducted a 12-year retrospective review of vulvar basal cell carcinoma (BCC) in a Chinese population. Study Design Medical records and histopathologic reports were examined from 5 major Hospitals in Hong Kong to list all patients diagnosed with vulvar BCC. Clinical data and histologic materials were reviewed. Results Sixteen vulvar BCCs were diagnosed. Most of them were pigmented. They were removed by simple excision or wide local excision. All the carcinomas were identified in the reticular dermis. The predominant histologic pattern was nodular, which may be mistaken as adenoid cystic carcinoma. Conclusion The high proportion of pigmented vulvar BCCs suggested that biopsy should be performed for any pigmented lesion in a Chinese patient. The BCCs are superficial and tissue-preserving treatment approach is recommended. The tumor depth estimation is difficult and intraoperative frozen section consultation may be helpful. Formal histopathologic assessment should be used to reach an objective diagnosis.

Breast carcinoma is the most common malignancy in women worldwide. Though fine needle aspiration cytology (FNAC) plays an important role in preoperative diagnosis, there may be diagnostic delays in affected young women due to a lower index of suspicion.The files of the Departments of Pathology, Singapore General Hospital, Singapore, and Prince of Wales Hospital, Hong Kong, were searched for cases of breast carcinoma in women aged 35 years or less. Those with prior FNA procedures comprised our study group. The FNA smears were reviewed and classified into five categories: inadequate, benign, equivocal, suspicious, malignant. The findings were correlated with subsequent histology.Thirty-four women aged 35 years and below underwent 35 FNACs, with one woman having bilateral FNA procedures. Upon review, one (2.9%) was classified as inadequate, one (2.9%) benign, five (14.3%) equivocal, five (14.3%) suspicious, 21 (60%) malignant and slides were not available for review for two (5.6%) cases. For six benign and equivocal cytological diagnoses, subsequent histology disclosed pure ductal carcinoma in situ (DCIS, 1 case), mucocoele-like lesions with DCIS (2 cases), invasive and in situ ductal carcinoma with neuroendocrine features (1 case) and two cases of invasive ductal carcinoma.Diagnostic difficulties in cytological interpretation of aspirates from breast carcinoma in young women may lead to unwanted delays, which occurred in six (17.6%) of 34 women in our series. Low grade cancers posing a pitfall in cytological diagnosis have to be considered.

Mammary phyllodes tumors are uncommon stromal-epithelial neoplasms, and are divided into benign, borderline malignant and frankly malignant groups on the basis of their histological features. Accumulating evidence shows that epidermal growth factor receptor (EGFR) is involved in the pathogenesis and progression of many malignancies. This study investigated 453 phyllodes tumors (296 benign, 98 borderline, 59 malignant) for EGFR expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for gene amplification. The staining was correlated to tumor margin status, degree of malignancy, stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. Cases with strong positive IHC staining were selected for FISH. The overall positive rate for EGFR was 16.2% (48/296), 30.6% (30/98) and 56% (33/59) for benign, borderline malignant and frankly malignant phyllodes tumors, respectively. FISH demonstrated egfr gene amplification in 8% of immunohistochemically positive cases. The results of this study provide strong evidence that EGFR overexpression is involved in the pathogenesis of phyllodes tumors, although gene amplification may not be the major underlying mechanism for overexpression.

Spindle cell lesions of the breast represent an interesting diagnostic problem, as the differential diagnoses are wide. Diagnosing this is particularly problematic but important when encountered in a needle core biopsy, as treatments of different entities are different. In the histologic assessment of spindle cell lesions, the simplified approach is to evaluate the spindle cells and the accompanying epithelial cells. In the biphasic lesions with predominance of spindle cells with benign epithelial component, fibroepithelial lesions including fibroadenomas and phyllodes tumors are the most common, followed by pseudoangiomatous stromal hyperplasia, hamartoma and adenomyoepithelioma. For biphasic lesions with predominance of spindle cells with malignant epithelial component, the biphasic metaplastic carcinoma is likely. For monophasic lesions with pure pleomorphic spindle cell only, the monophasic metaplastic carcinoma is more common than the rare primary sarcomas like malignant fibrous histiocytoma, angiosarcoma, and other high grade sarcomas. In monophasic lesions with pure bland spindle cells only, the possible lesions include fibromatosis, fibromatosis like metaplastic carcinoma and other unusual conditions like dermatofibrosarcoma protuberance. By careful searching for the accompanying epithelial element, and with the aid of appropriate clinical input and judicious use of immunohistochemistry, many of these lesions can be confidently diagnosed in the needle core biopsy, thus facilitating appropriate treatments.

Background and Aims: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. Method: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. Results: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. Conclusion: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours.

Background: Chordoid meningioma is a rare meningioma variant characterised by epithelioid cord-like tumour cells in a myxoid stroma. It is classified as grade II (World Health Organization) tumours, as they have a tendency to behave more aggressively than traditional meningiomas and have a greater likelihood of recurrence. Aims: To report the features of intraoperative imprint smears of five cases of chordoid meningioma. Methods: The intraoperative squash smears were reviewed for cellularity, cellular atypia, mitotic figure, cytoplasmic vacuolation, intranuclear inclusion, presence of a cohesive cord of tumour cells, whorl-like structure, psammoma bodies, chronic inflammatory cells (lymphocytes and plasma cells), background mucin and necrosis. Results: All cases were of moderate to high cellularity, with cohesive cords of bland tumour cells possessing uniformly round nuclei with smooth nuclear outline, stippled chromatin and small nucleoli, with cytoplasmic vacuolation and chronic inflammatory cells in the background. Intranuclear inclusions (80%) and whorl-like structures (60%) were also common. Necrotic background, psammoma bodies or mitotic figures were consistently absent. Conclusions: The cytological features of chordoid mengiomas are distinctive, and intraoperative imprint diagnosis is feasible.

Background: Metaplastic carcinoma of the breast encompasses a heterogeneous group of tumours with variable components of sarcomatoid, squamous or poorly differentiated carcinomas. Aim: To review a series of 19 cytological preparations of metaplastic carcinomas to assess diagnostic cytological features. Methods: 17 cases of fine-needle aspirates of histologically proven metaplastic carcinomas (4 monophasic spindle cell carcinomas, 4 squamous cell carcinomas and 11 biphasic tumours) were reviewed, with an emphasis on the presence of poorly differentiated carcinoma, squamous cell carcinoma, atypical spindle cells, benign stromal fragments and necrosis. Results: All cases were diagnosed as malignant, with 68% of cases showing moderate to high cellularity, and 47% showing necrosis. If the tumours were analysed according to the constituting components histologically, 7, 15 and 8 cases, respectively, possess poorly differentiated carcinoma cells, sarcomatoid malignant cells and squamous carcinoma cells, whereas these components were cytologically identified in 11, 10 and 7 cases, respectively. Dual tumour populations were identified in only 5 of the 11 biphasic carcinomas in the cytological preparations; and the stromal material was cytologically identified in the only case with chondroid stroma. Conclusions: Identification of metaplastic carcinoma in cytology remains problematic. There seems to be morphological overlap between various components. The identification of dual components, unequivocal squamous carcinoma cells and chondroid stroma is helpful for diagnosis, but it is uncommon. The presence of poorly differentiated carcinoma cells with a suggestion of focal spindle morphology is another clue to the suggestion of metaplastic carcinoma.

Background: Mammary metaplastic carcinoma encompasses epithelial-only carcinoma (high-grade adenosquamous carcinoma or pure squamous cell carcinoma), biphasic epithelial and sarcomatoid carcinoma and monophasic spindle cell carcinoma. Aim: To evaluate the clinicopathological features of a large series of 34 metaplastic carcinomas. Methods: 10 epithelial-only, 14 biphasic and 10 monophasic metaplastic carcinomas were assessed for nuclear grade, hormone receptor status, HER2/neu (cerbB2) oncogene expression, Ki-67 and p53, lymph node status and recurrence on follow-up. Results: Intermediate to high nuclear grade were assessed in most (33/34) tumours. Oestrogen and progesterone receptors were negative in 8 of 10 epithelial-only, all 14 biphasic, and 9 of 10 monophasic tumours, cerbB2 was negative in 7 of 10 epithelial-only, all 14 biphasic and 8 of 10 monophasic tumours. Ki-67 was found to be positive in 6 of 10 epithelial-only, 6 of 14 biphasic, and 7 of 10 monophasic tumours, whereas p53 was positive in 6 of 10 epithelial-only, 7 of 14 biphasic, and 8 of 10 monophasic tumours. Lymph node metastases were seen in 7 of 7 epithelial-only, 7 of 11 biphasic, and 3 of 7 monophasic tumours. Recurrences were seen in 4 of 7 epithelial-only, 8 of 9 biphasic, and 4 of 9 monophasic tumours. Conclusions: All three subtypes of metaplastic carcinoma are known to behave aggressively, and should be differentiated from the low-grade fibromatosis-like metaplastic carcinoma, which does not metastasise. Oncological treatment options may be limited by the frequently negative status of hormonal receptor and cerbB2.

Background/Aims: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. Methods: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. Results: There was a progressive increase in the patients’ age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. Conclusions: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon lesion usually found in premenopausal women. Histologically, it is characterized by complex, anatomosing, empty slit-like spaces in a dense collagenous stroma. These pseudoangiomatous spaces are lined by monomorphic spindle cells of myofibroblastic differentiation. Cytological features of PASH are rarely discussed and reported, and may pose diagnostic challenge to surgical pathologists. Two cases of PASH are reported with emphasis on the FNAC features and cytologic differentiation from other benign fibroepithelial lesions.

Mammary phyllodes tumors are uncommon stromal neoplasms, and are divided into benign, borderline and malignant groups basing on histologic criteria. While benign phyllodes tumors may recur, borderline phyllodes tumors show higher propensity to recur locally and rarely metastasize, and malignant phyllodes tumors show even higher chances of local recurrences or distant metastases. c-kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117) and is a marker for gastrointestinal stromal tumors (GIST). With the advent of therapeutic agent targeted at this receptor for GIST, we investigated 179 phyllodes tumors (101 benign, 50 borderline, 28 malignant) for c-kit expression using immunohistochemistry. The staining was compared to the degree of malignancy, and to the degree of stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. The overall positive rate for c-kit was 29% (52/179) and 17% (17/101), 24% (12/50) and 46% (13/28), respectively, for benign, borderline malignant and frank malignant phyllodes and the differences between all categories were significant (chi2=13.844, P=0.001). In mammary phyllodes tumors, there was increasing c-kit expression with increasing degree of malignancy, up to 46% in malignant cases. This provides strong evidence that c-kit receptor mediated tyrosine kinase involvement in the pathogenesis of phyllodes tumors, and the therapeutic agent, STI571, Glivec, may be a potentially useful drug for its management.

Aims: Myospherulosis is a rare condition characterised by sac-like structures containing spheroid bodies in cysts or cystic spaces in the tissue. This condition has not previously been reported in the liver. The association with previous portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil and the proposed mechanism of pathogenesis are discussed. Methods: Samples from 8 patients treated by hepatectomy after portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil were retrieved from the archives of the United Christian Hospital, Hong Kong. The histological specimens were reviewed. A panel of histochemical and immunohistochemical stains was used. Results: All cases showed hepatic myospherulosis within the veins. The veins were denuded of endothelium, which was replaced by granulation tissue and fibrous tissue with a lymphoplasmacytic infiltrate. Foreign body-type giant cells (six cases) and eosinophilic infiltrates (seven cases) were noted in most cases. Both parent bodies and endobodies were stained red by Papanicolaou and Masson’s trichrome and stained blue by solochrome cyanine. The endobodies showed immunoreactivity towards glycophorin A. They were negative for Alcian blue, periodic acid Schiff, Grocott, and Ziehl-Neelsen stains. Conclusions: The endobodies of myospherulosis may be misdiagnosed as fungi or algae by the unwary. The clinical history, intravascular location, lack of staining with periodic acid Schiff and Grocott stains, and positive glycophorin A staining are generally sufficient for a confident diagnosis of myospherulosis.

We examined 186 phyllodes tumors (106 benign, 51 borderline, 29 malignant) for angiogenesis by assessing stromal microvessel density by the hot spot method and assessing p53 protein expression; we correlated these factors with stromal cellularity, margin status, nuclear pleomorphism, mitosis, and stromal overgrowth. Increased degree of malignancy in phyllodes tumors is associated with increased patient age and tumor size. Microvessel density and p53 protein expression also showed a similar increase with malignancy. Using a logistic regression model, microvessel density was shown to be useful in predicting malignancy in phyllodes tumors, independent of key criteria of stromal overgrowth, nuclear pleomorphism, and mitosis. Microvessel density showed correlation with stromal cellularity and margin status, suggesting an interrelationship between these parameters. P53 protein expression showed a positive correlation with microvessel density, suggesting possible overlap in the underlying mechanism of these two factors in the pathogenesis of phyllodes tumors. The numbers of recurrences and metastases are small in our series, and no significant difference was demonstrated in microvessel density and p53 protein expression compared with the primary. We conclude that microvessel density and p53 are useful as independent criteria in evaluating malignancy in phyllodes tumors.

We report the cytology findings of a rare case of myxoid leiomyosarcoma of the uterus with intraabdominal dissemination. The cytology showed uniformly dispersed spindly to polygonal "epithelioid" tumor cells focally linked by background matrix. Spindly tumor cells attaching to and radiating from branching capillary structures were also present. Occasionally, scattered "signet-ring" cells were found, mimicking metastatic poorly differentiated adenocarcinoma. The background mucoid substance was more conspicuous in the cell block sections. Gross and histologic examination of the surgical specimen revealed a large uterine leiomyosarcoma with prominent myxoid change. Ultrastructural study showed that the "signet-ring" appearance was mainly due to degenerative cytoplasmic change with ballooning of mitochondria, dilatation of endoplasmic reticulum, and elevation of outer nuclear membrane. In contrast to other spindle cell malignancies such as sarcomatoid mesothelioma, sarcomatoid carcinoma, or malignant melanoma, true sarcoma cells in general carry a distinctive cytologic appearance in washing/effusion fluid. In a correct clinical setting, the peculiar association with mucoid matrix and absence of classic lipoblasts should also raise the suspicion of metastatic myxoid leiomyosarcoma.

7667 Background: EGFR mutation is a diverse and complex phenomenon. Shigematsu et al (JNCI 97:339,2005), analyzing NSCLC samples from multiple ethnicities and histologic cell types, reported 11 types of in-frame deletions in exon 19 (46%), 9 missense mutation in exons 18, 20, 21 (45%) and 8 in-frame insertion in exons 20 (9%). 3/130 tumors (2.3%) had multiple mutations. Here we report the incidence, mutation pattern and novel finding of EGFR mutation in a homogenous ethnic group with adenocarcinoma of lung. Methods: Between 2004 and 2006 we isolated genomic DNA from 194 (archival 53, prospective 141) primary lung adenocarinoma for PCR amplification of EGFR exon 18–21. We isolated tumor cell by micro-dissection. PCR products were purified and sequenced using the BigDye Terminator Cycly Sequencing Ready Reaction Kit (Applied Biosystem) and run on Applied Biosystem 3100 Genetic Analyzer. Results: We found 79 EGFR mutations in 73 tumors (37.6%). Six (8.2%) had double mutations. IN-FRAME DEL: 10 types in exon 19 (39 cases, 49.4%); 1 type in exon 18 (1 case). MISSENSE MUTATION: 2 types in exon 18 (2 cases); 4 types in exon 20 (5 cases) and 2 types in exon 21 (29 cases, 36.7%) IN-FRAME INSERTION: 3 types in exon 20 (3 cases). Typical exon 19 E746-A750del and exon 21 L858R mutations accounted for 31% and 34%, respectively. We found 11 types of mutations not previously described.( Table ) Four pts with novel mutations received EGFR TKI and 3 attained PR (all with exon 19 del). Two pts have T790M mutations without prior exposure to EGFR TKI and both with double mutations. Conclusion: Mutation pattern of EGFR gene in Chinese pts with adenocarcinoma is similar to the Shigematsu report. The overall incidence of EGFR mutation and multiple mutations are higher but in-frame insertion in exon 20 is less common. Majority of the novel mutations are rare mutations involving exon 18 and 20. No significant financial relationships to disclose. [Table: see text]