Staging nodal metastases in nasopharyngeal carcinoma: which method should be used to measure nodal dimension on MRI?

AIM: To investigate four methods to measure the maximum dimension (MD) of metastatic neck nodes and correlate with clinical outcome in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Magnetic resonance imaging (MRI) examinations of 712 NPC patients were analysed. MD measurements using methods 1, 2, 3, and 4 were obtained from a single node in the axial plane; a single node in the axial/coronal plane; a single and/or confluent nodes in the axial/coronal plane; and a single and/or confluent and/or contiguous nodes in the axial/coronal plane, respectively. MDs obtained from the four methods were correlated with nodal volume (NV) using Pearson's correlation test. MDs obtained from the four methods, T and N stages, age, gender, and treatment were correlated with overall survival (OS), disease-specific survival (DSS), distant metastases free survival (DMFS), and regional relapse-free survival (RRFS) using cox regression. RESULTS: Method 4 (R: 0.84) had the strongest correlation with NV followed by method 3 (R: 0.77), method 2 (R: 0.70) and method 1(R: 0.69). Method 4 was the only independent nodal measurement of OS, DSS, and DMFS (p-values = 0.008, <0.001 and <0.001, respectively). None of the MD methods was an independent measurement of RRFS. CONCLUSIONS: The best method to obtain the MD for staging incorporates not only single and confluent, but also contiguous metastatic nodes measured in the plane with the MD.

Identification of a PP2A-interacting protein that functions as a negative regulator of phosphatase activity in the ATM/ATR signaling pathway.

Protein serine/threonine phosphatase 2A (PP2A) activity must be tightly controlled to maintain cell homeostasis. Here, we report the identification of a previously uncharacterized mammalian protein, type 2A-interacting protein (TIP), as a novel regulatory protein of PP2A and the PP2A-like enzymes PP4 and PP6. TIP is a ubiquitously expressed protein and parallels the distribution of the PP2A catalytic subunit. Unlike its role in yeast, TIP does not interact with the mammalian homolog of type 2A-associated protein of 42 kDa (Tap42), alpha4, but instead associates with PP2A, PP4 and PP6 catalytic subunits independently of mammalian target of rapamycin kinase activity. Interestingly, the 20 kDa TIP splice variant TIP_i2, which lacks amino acids 173-272 of TIP's C-terminus, does not interact with PP2A; this finding indicates that residues 173-272 are important for the assembly of the TIP.phosphatase complex. In contrast to purified PP2A holoenzymes, TIP.PP2A complexes are devoid of phosphatase activity. Furthermore, alterations in the cellular levels of TIP influence the phosphorylation state of a specific protein substrate of ataxia-telangiectasia mutated (ATM)/ATM- and Rad3-related (ATR) kinases. Elevated levels of TIP result in an increase in the phosphorylation state of this protein substrate, whereas TIP-depleted cells exhibit a significant decrease in this protein's phosphorylation state, which is reversed by treatment with the PP2A inhibitor okadaic acid. These results indicate TIP is a novel inhibitory regulator of PP2A and implicate a role for TIP.PP2A complexes within the ATM/ATR signaling pathway controlling DNA replication and repair.

MR Imaging Criteria for the Detection of Nasopharyngeal Carcinoma: Discrimination of Early-Stage Primary Tumors from Benign Hyperplasia.

BACKGROUND AND PURPOSE: MR imaging can detect nasopharyngeal carcinoma that is hidden from endoscopic view, but for accurate detection carcinoma confined within the nasopharynx (stage T1) must be distinguished from benign hyperplasia of the nasopharynx. This study aimed to document the MR imaging features of stage T1 nasopharyngeal carcinoma and to attempt to identify features distinguishing it from benign hyperplasia. MATERIALS AND METHODS: MR images of 189 patients with nasopharyngeal carcinoma confined to the nasopharynx and those of 144 patients with benign hyperplasia were reviewed and compared in this retrospective study. The center, volume, size asymmetry (maximum percentage difference in area between the right and left nasopharyngeal halves), signal intensity asymmetry, deep mucosal white line (greater contrast enhancement along the deep tumor margin), and absence/distortion of the adenoidal septa were evaluated. Differences were assessed with logistic regression and the χ2 test. RESULTS: The nasopharyngeal carcinoma center was lateral, central, or diffuse in 134/189 (70.9%), 25/189 (13.2%), and 30/189 (15.9%) cases, respectively. Nasopharyngeal carcinomas involving the walls showed that a deep mucosal white line was present in 180/183 (98.4%), with a focal loss of this line in 153/180 (85%) cases. Adenoidal septa were absent or distorted in 111/111 (100%) nasopharyngeal carcinomas involving the adenoid. Compared with benign hyperplasia, nasopharyngeal carcinoma had a significantly greater volume, size asymmetry, signal asymmetry, focal loss of the deep mucosal white line, and absence/distortion of the adenoidal septa (P < .001). Although size asymmetry was the most accurate criterion (89.5%) for nasopharyngeal carcinoma detection, use of this parameter alone would have missed 11.9% of early-stage T1 nasopharyngeal carcinomas. CONCLUSIONS: MR imaging features can help distinguish stage T1 nasopharyngeal carcinoma from benign hyperplasia in most cases.

The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast.

BACKGROUND: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. METHODS: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. RESULTS: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). CONCLUSIONS: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.

Metaplastic carcinoma of the breast: a clinicopathological review.

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 metastasize. Oncological treatment options may be limited by the frequently negative status of hormonal receptor and cerbB2.

[Arthroscopic volar wrist ganglionectomy]. / Résection des kystes synoviaux palmaires par arthroscopie.

As an original technique developed by our department, the preliminary result of arthroscopic resection of volar wrist ganglion was first published in 2003. Since then, there were few reports in the literature concerning this new treatment method. The aim of the study is to evaluate the long-term outcome of this treatment technique. From August 1997 to April 2005, 21 volar wrist ganglia with average size of 2 cm (range 1-4 cm) were treated. The average age of patients was 48.6 (range 18-63). Thirteen ganglia had previous treatment including either aspiration or open excision. Seventy-one percent of the operations were performed under local anesthesia. Wrist arthrogram was performed in 9 cases. Seven cases showed origin from radiocarpal joint and all proceeded to arthroscopic resection successfully. Arthroscopically, 75% of ganglia arose from the interval between radioscaphocapitate and long radiolunate ligament, and 25% from the interval between long radiolunate and short radiolunate ligament. Sixteen of the 21 ganglia could be excised by arthroscopic technique. The average follow up was 56 months (range 9-101 months). There were 2 recurrences. One was treated with repeated arthroscopic excision and the other by open excision. There was no impairment of wrist motion and function in all patients. No neurovascular complication was encountered. Arthroscopic resection was an effective treatment method for well-selected volar wrist ganglion arising from the radiocarpal joint in long run.

Diffusion-Weighted Imaging of Nasopharyngeal Carcinoma: Can Pretreatment DWI Predict Local Failure Based on Long-Term Outcome?

BACKGROUND AND PURPOSE: Pretreatment prediction of patients with nasopharyngeal carcinoma who will fail conventional treatment would potentially allow these patients to undergo more intensive treatment or closer posttreatment monitoring. The aim of the study was to determine the ability of pretreatment DWI to predict local failure in patients with nasopharyngeal carcinoma based on long-term clinical outcome. MATERIALS AND METHODS: One hundred fifty-eight patients with pretreatment DWI underwent analysis of the primary tumor to obtain the ADC mean, ADC skewness, ADC kurtosis, volume, and T-stage. Univariate and multivariate analyses using logistic regression were performed to compare the ADC parameters, volume, T-stage, and patient age in primary tumors with local failure and those with local control, by using a minimum of 5-year follow-up to confirm local control. RESULTS: Local control was achieved in 131/158 (83%) patients (range, 60.3-117.7 months) and local failure occurred in 27/158 (17%) patients (range, 5.2-79.8 months). Compared with tumors with local control, those with local failure showed a significantly lower ADC skewness (ADC values with the greatest frequencies were shifted away from the lower ADC range) (P = .006) and lower ADC kurtosis (curve peak broader) (P = .024). The ADC skewness remained significant on multivariate analysis (P = .044). There was a trend toward higher tumor volumes in local failure, but the volume, together with T-stage and ADC mean, were not significantly different between the 2 groups. CONCLUSIONS: Pretreatment DWI of primary tumors found that the skewness of the ADC distribution curve was a predictor of local failure in patients with nasopharyngeal carcinoma, based on long-term clinical outcome.

Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.

Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. The role of Sirtuin 1 (SIRT1) in hepatic I/R injury remains elusive. Using human and mouse livers, we investigated the effects of I/R on hepatocellular SIRT1. SIRT1 expression was significantly decreased after I/R. Genetic overexpression or pharmacological activation of SIRT1 markedly suppressed defective autophagy, onset of the mitochondrial permeability transition, and hepatocyte death after I/R, whereas SIRT1-null hepatocytes exhibited increased sensitivity to I/R injury. Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1. Moreover, SIRT1 overexpression substantially increased autophagy in wild-type cells, but not in MFN2-deficient cells. Thus, our results demonstrate that the loss of SIRT1 causes a sequential chain of defective autophagy, mitochondrial dysfunction, and hepatocyte death after I/R.

Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-(beta) in mesenchymal chondroprogenitor cell growth.

Cartilage formation is driven by mesenchymal chondroprogenitor cells (MCCs) that proliferate and differentiate into chondrocytes. The molecular mechanisms by which growth factors regulate MCC fate are not well defined. Insulin-like growth factor binding protein-3 (IGFBP-3) has intrinsic bioactivity that is independent of IGF binding. We previously reported that IGFBP-3 has IGF-independent antiproliferative and apoptotic effects in MCCs, and requires STAT-1 activation to mediate its apoptotic effect. Transforming growth factor-beta (TGF-beta) is a key chondroinductive growth factor. The objective of the study is to define the interactions between IGFBP-3 and TGF-beta in MCC growth and their intracellular signaling pathways. We used the RCJ3*1C5*18 mesenchymal chondrogenic cells that without biochemical or oncogenic transformation progress in culture from MCCs to differentiated chondrocytes. Cell proliferation was assessed in MCCs treated with IGFBP-3 or transfected with IGFBP-3, in the presence or absence of TGF-beta. To demonstrate that IGFBP-3 effects were IGF-independent an IGFBP-3 analog that lacks IGF binding was used (GGG-IGFBP-3). To determine the functional roles of the TGF-beta-mediated signaling and the STAT-1 pathway, cells were either stably transfected with a dominant negative TGF-beta type II receptor (MCC-DNTbetaRII) or treated with a STAT-1 morpholino antisense oligonucleotide. We found that in MCCs, TGF-beta antagonized the antiproliferative effect of IGFBP-3. IGFBP-3 increased the cyclin-dependent kinase inhibitor p21 expression and this effect was abolished by TGF-beta. Furthermore, TGF-beta inhibited STAT-1 phosphorylation induced by IGFBP-3. Similarly to TGF-beta, STAT-1 antisense oligonucleotide inhibited the IGFBP-3 antiproliferative action. Although TGF-beta in MCC-DNTbetaRII lacked Smad-mediated signaling, it persistently antagonized the IGFBP-3 antiproliferative action. However, TGF-beta even in MCC-DNTbetaRII cells induced ERK1/2 phosphorylation, and treatment with MEK inhibitor, UO126, inhibited the antagonistic effects of TGF-beta on IGFBP-3. Furthermore, UO126 blocked the TGF-beta inhibition of STAT-1 phosphorylation induced by IGFBP-3. Collectively, these results demonstrate cross-talk between the IGFBP-3-dependent STAT-1 signaling and the TGF-beta-dependent ERK pathway that regulates MCC proliferation.

CD44s is useful in the differentiation of benign and malignant papillary lesions of the breast.

BACKGROUND/AIMS: CD44s, the standard form of CD44, has been shown to be downregulated during malignant transformation of breast cancers. It has also been reported recently to be a useful marker in differentiating between benign and malignant papillary lesions of the breast, with high expression in the former. CD44s expression in benign and malignant papillary lesions was evaluated. METHODS: CD44s expression was assessed by immunohistochemistry in 101 benign papillomas and 59 papillary carcinomas (seven invasive papillary carcinomas, 41 papillary ductal carcinomas in situ, and 11 ductal carcinomas involving papillomas). RESULTS: Patients' age and tumour size were significantly different between the papilloma and papillary carcinoma groups (p < 0.0001). CD44s showed positive staining in 45 papillomas (45%) and five papillary carcinomas (8%), and the difference was significant (p < 0.0001). The myoepithelial cells, when present, were also positive for CD44s in both groups, with no observable differences. Using CD44s positive staining to differentiate between benign and malignant papillary lesions gives a sensitivity, specificity, and accuracy of 45%, 92%, and 62%, respectively. CONCLUSIONS: CD44s may be useful as an adjunct in the evaluation of morphologically problematic cases of papillary lesion of the breast.

Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours.

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.

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: 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. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: 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. RESULTS: 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 (p < 0.0001). 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. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Detection of Nasopharyngeal Carcinoma by MR Imaging: Diagnostic Accuracy of MRI Compared with Endoscopy and Endoscopic Biopsy Based on Long-Term Follow-Up.

BACKGROUND AND PURPOSE: Our previous nasopharyngeal carcinoma detection study, comparing MR imaging, endoscopy, and endoscopic biopsy, showed that MR imaging is a highly sensitive test that identifies nasopharyngeal carcinomas missed by endoscopy. However, at the close of that study, patients without biopsy-proved nasopharyngeal carcinoma nevertheless had shown suspicious abnormalities on endoscopy and/or MR imaging. The aim of this study was to determine whether there were any patients with undiagnosed nasopharyngeal carcinoma by obtaining long-term follow-up and to use these data to re-evaluate the diagnostic performance of MR imaging. MATERIALS AND METHODS: In the previous study, 246 patients referred to a hospital ear, nose, and throat clinic with suspected nasopharyngeal carcinoma, based on a wide range of clinical indications, had undergone MR imaging, endoscopy, and endoscopic biopsy, and 77 had biopsy-proved nasopharyngeal carcinoma. One hundred twenty-six of 169 patients without biopsy-proved nasopharyngeal carcinoma underwent re-examination of the nasopharynx after a minimum of 3 years, including 17 patients in whom a previous examination (MR imaging = 11; endoscopy = 7) had been positive for nasopharyngeal carcinoma, but the biopsy had been negative for it. Patients with nasopharyngeal carcinoma were identified by biopsy obtained in the previous and this follow-up study; patients without nasopharyngeal carcinoma were identified by the absence of a tumor on re-examination of the nasopharynx. The sensitivity and specificity of the previous investigations were updated and compared by using the Fisher exact test. RESULTS: One patient with a previous positive MR imaging finding was subsequently proved to have nasopharyngeal carcinoma. Nasopharyngeal carcinomas were not found in the remaining 125 patients at follow-up, and the previous positive findings for nasopharyngeal carcinoma on MR imaging and endoscopy were attributed to benign lymphoid hyperplasia. The diagnostic performances for the previous MR imaging, endoscopy, and endoscopic biopsy were 100%, 88%, and 94%, respectively, for sensitivity, and 92%, 94%, and 100%, respectively, for specificity; the differences between MR imaging and endoscopy were significant for sensitivity (P = .003) but not specificity (P = .617). CONCLUSIONS: MR imaging detected the 12% of nasopharyngeal carcinomas that were endoscopically invisible, including 1 cancer that remained endoscopically occult for several years. Lymphoid hyperplasia reduced the specificity of MR imaging.

Induction of the C/EBP homologous protein (CHOP) by amino acid deprivation requires insulin-like growth factor I, phosphatidylinositol 3-kinase, and mammalian target of rapamycin signaling.

In mammalian cells, gene regulation by amino acid deprivation is poorly understood. Here, we examined the signaling pathways involved in the induction of the C/EBP homologous protein (CHOP) by amino acid starvation. CHOP is a transcription factor that heterodimerizes with other C/EBP family members and may inhibit or activate the transcription of target genes depending on their sequence-specific elements. Amino acid deficiency, when accompanied by insulin-like growth factor I signaling, results in the accumulation of CHOP messenger RNA and protein in AKR-2B and NIH-3T3 cells. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 are able to block CHOP induction in response to amino acid deprivation. Rapamycin is also able to abrogate CHOP expression, suggesting that the mammalian target of rapamycin is involved in CHOP induction by amino acid deficiency. LY294002 and rapamycin are also able to block CHOP induction by hydrogen peroxide, but do not affect expression induced by sodium arsenite or A23187. This is the first evidence that the insulin-like growth factor I/phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway is required for gene regulation by amino acid deprivation and that this pathway is involved in the induction of CHOP by both amino acid deficiency and oxidative stress by hydrogen peroxide.

Ductal carcinoma in situ arising in mammary hamartoma.

Hamartoma of the breast is an uncommon lesion. Although it can possess characteristic radiological features, the pathological appearance is not distinctive. Hamartoma is generally considered benign, but four cases have been reported with ductal and lobular carcinoma arising in hamartomas. This report describes further cases of hamartoma from which ductal carcinoma in situ arose, with one showing early invasion. In both cases, the tumours were within the hamartomas and were adequately excised during lumpectomies of the hamartomas, and the patients were well afterwards. This report emphasises the importance of adequate sampling of mammary hamartoma.

Fine needle aspiration cytology of granulomatous mastitis.

AIMS: Granulomatous mastitis (GM) is an uncommon breast lesion that mimics carcinoma. The fine needle aspiration cytological (FNAC) features of GM have rarely been discussed in the literature. These features are reported in eight histologically confirmed cases of GM. METHODS: A retrospective study was undertaken in which a diagnosis of GM had been made on histopathology, and the FNAC slides were reviewed and assessed for the presence of granulomas, necrosis, multinucleated giant cells, and inflammatory background cells. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis was performed on the histological material to exclude tuberculosis. RESULTS: All cases were confirmed histologically and PCR for mycobacterial DNA was negative. In the FNACs, varying numbers of granulomas composed of epithelioid histiocytes were present in four cases. The same four cases showed giant cells of either foreign body or Langhan's type. No necrosis was noted. Six cases showed many histiocytes, some plump and others epithelioid, in the background. The number of epithelioid histiocytes corresponded to the presence of granulomas. Neutrophils were the predominant background inflammatory cells in most cases (six). CONCLUSIONS: The cytological diagnosis of GM is difficult because the features overlap with other aetiologies, including tuberculosis. Specific features are absent. The absence of necrosis and a predominantly neutrophilic infiltrate in the background favour a diagnosis of GM. This diagnosis should also be considered when abundant epithelioid histiocytes are seen in smears, even in the absence of granulomas. However, the definitive diagnosis of GM depends on histology from fine needle biopsies and negative microbiological investigations.

Hamartoma of the breast: a clinicopathological review.

AIMS: To review 25 cases of breast hamartoma and discuss the pathological criteria, and the usefulness of imaging modalities, fine needle aspiration cytology (FNAC), and needle core biopsy in the diagnosis. METHODS: The hamartomas were assessed for interlobular fibrotic stroma, stromal adipose tissue content, pseudo-angiomatous stromal hyperplasia, and epithelial changes (hyperplasia, adenosis or apocrine metaplasia, and cyst formation). All imagings, previous FNACs, and biopsies were also reviewed. RESULTS: Imaging (mammography, ultrasound, and magnetic resonance imaging) was performed in 18 cases, and mostly showed encapsulated masses with a heterogeneous appearance. Microscopically, all hamartomas demonstrated good demarcation with fibrous tissue condensation. Adipose tissue was noted in all cases (5-90%; mean, 31%), and interlobular fibrosis in 21 cases. Benign epithelial hyperplasia occurred in 10 cases, and pseudo-angiomatous stromal hyperplasia or cystic ducts in eight cases each. Apocrine metaplasia, calcification, stromal giant cells, and adenosis occurred in four cases or less. Two cases showed coexisting ductal carcinoma in situ limited to within the hamartoma. Needle core biopsies (four cases) and FNAC (14 cases) were largely insufficient, inconclusive, or non-specific. CONCLUSIONS: Hamartomas do not possess specific diagnostic histological features. The role of FNAC and needle core biopsy in making the diagnosis is limited, and requires clinical and radiological correlation to avoid underdiagnosis.

Multinucleated stromal giant cells in mammary phyllodes tumours.

Mammary phyllodes tumour (PT) is an uncommon fibroepithelial neoplasm with a prominent stromal component. We report five cases of PT (one benign, three borderline, one malignant) with giant cells in the stroma. All occurred in adults and ranged from 1.8 to 4.0 cm in size. The overall cellularity, stromal cell pleomorphism and mitotic count was higher for the malignant and borderline than the benign PT. The giant cell number ranged from 18 to 35 cells per 10 high power fields, but there was no relationship between this number and the grade of the PT. Most giant cells were subepithelial, with multiple nuclei arranged in a linear or irregular pattern, and moderate amount of cytoplasm. The immunohistochemical profile of the giant cells was similar to the stromal cells. In all cases, both giant cells and stromal cells expressed vimentin strongly but not desmin; in two cases, both cell populations expressed actin weakly. The respective percentage of giant cells and stromal cells expressing MIB1 was also similar. This suggests that these giant cells do not represent a different, more active stromal population, despite the more bizarre appearance. In view of the small number of cases, the significance of such giant cells on the prognosis of PT remains uncertain.

Subfascial endoscopic perforator vein surgery (SEPS) using the ultrasonic scalpel.

Subfascial endoscopic perforator vein surgery (SEPS) was recently introduced as a minimally invasive method to ligate incompetent perforating veins in patients with severe chronic venous insufficiency of the lower extremities. Herein we describe a technique in which we used a 5-mm ultrasonic scalpel for the transection of perforating veins in 16 SEPS performed in 14 patients. The use of the ultrasonic scalpel allowed for the precise coagulation and transection of the perforator vein with hemostasis, while avoiding the use of metal clips. Our initial results showed that the technique was feasible with minimal morbidity. We recommend the use of the ultrasonic scalpel as an alternative tool to transect perforating veins in SEPS.

Outpatient laparoscopic cholecystectomy in Hong Kong: patient acceptance.

The authors performed a prospective evaluation of 60 Hong Kong Chinese patients with symptomatic gallstones and gallbladder polyps undergoing outpatient laparoscopic cholecystectomy in a regional hospital in Hong Kong from March 1996 to May 1998 to determine the feasibility, satisfaction, and acceptance of this procedure among Chinese patients. Patients with American Society of Anesthesiologists grade I and II gallstones or polyps were selected. Exclusion criteria included 1) history of upper abdominal operations, attacks of acute cholecystitis, cholangitis, or pancreatitis; 2) abnormal liver function; and 3) ultrasonographic evidence of contracted gallbladder, thickened gallbladder wall, dilated common bile duct, or common bile duct stones. Patients discharged at 5:00 PM on the day of cholecystectomy were defined as having undergone outpatient procedure. Patients were asked about procedure acceptance, rated on a scale of 1 to 10 (best), using a standardized questionnaire 4 weeks after operation. The study included 21 men and 39 women with mean age of 40.5 years (range, 27-59). There were no conversions to open procedures in the series. There were 6 (10%) unanticipated postoperative hospital admissions; all patients were discharged on the first postoperative day. Another patient was readmitted 3 days after operation because of a common bile duct stone. Overall patient acceptance of outpatient laparoscopic cholecystectomy was good, with a mean score of 8.6 of 10. Thirteen patients (22%) expressed dissatisfaction with being discharged earlier than they had expected, and 9 (15%) would have preferred inpatient care. Forty-eight patients (80%) resumed full daily activities by the first postoperative day; the remaining 12 did so by the end of the first week. Among the 44 working patients, only 4 (9%) resumed full duty within the first postoperative week; 29 (66%) did so by the second week and the remaining 11 (25%) returned to work after the third week. By selecting appropriate subjects, outpatient laparoscopic cholecystectomy is feasible and highly accepted among Hong Kong Chinese patients. Approximately one quarter of the patients preferred a longer postoperative stay or inpatient care.