A case of nephrogenic diabetes insipidus likely caused by anti-neutrophil cytoplastic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a relatively rare form of autoimmune disease. Diabetes insipidus (DI) is characterized by diluted polyuria and thirstiness, and is clinically categorized into central and nephrogenic DI depending on damaged organs. In most previously reported cases, ANCA-related disorders have been implicated in central DI, which is attributed to impaired secretion of arginine vasopressin (AVP) from the posterior pituitary. However, no previous case of AAV-related nephrogenic DI has been reported in the English literature. Herein, we report a case of nephrogenic DI likely caused by AAV. A 76-year-old man was admitted to our hospital for acute kidney injury. He showed dehydration, polyuria, and polydipsia. Laboratory tests demonstrated elevated levels of serum urea and creatinine and a high myeloperoxidase ANCA titer. In the present case, both plasma AVP concentration and response of AVP secretion to 5% saline load test were normal. In addition, 1-desmino-8-arginine vasopressin administration could not increase urinary osmolarity. Kidney biopsy specimen revealed tubulointerstitial nephritis with findings that appeared to indicate peritubular capillaritis. Therefore, the patient was diagnosed with nephrogenic DI likely owing to ANCA-associated tubulointerstitial nephritis. Immediately after prednisolone administration, urinary volume decreased, urinary osmolarity increased, and kidney function was improved. This case demonstrates that AAV that extensively affects the tubulointerstitial area can result in nephrogenic DI.

Expression of matrix metalloproteinase-7 correlates with the invasion of T1 colorectal carcinoma.

T1 colorectal carcinomas (CRCs) are an initial site of metastatic spread. Various risk factors for lymph node metastasis have been investigated in T1 CRCs. However, the major step in the entire process of metastasis remains unclear. In terms of carcinoma invasion and metastasis, matrix metalloproteinases (MMPs) have recently gained increasing attention. Notably, MMP-7 is frequently overexpressed in CRCs, but its implication has not been determined in T1 CRCs yet. The present study aimed to clarify the associations between the pathological risk factors of T1 CRCs and MMP-7. In the current study, 211 lesions of T1 CRC that were resected endoscopically or surgically at Showa University Northern Yokohama Hospital (Yokohama, Japan) between April 2008 and December 2009 were retrospectively analyzed. MMP-7 was immunostained and evaluated by its frequency of expression. Pathological factors of T1 CRCs were analyzed in association with MMP-7 expression. Furthermore, the ultrastructural alterations of carcinoma invasion were examined using low vacuum-scanning electron microscopy (LV-SEM). MMP-7 expression was associated with venous invasion (P=0.005), and LV-SEM revealed the disappearance of the normal structure of collagen and elastic fibers of veins invaded by tumor cells expressing MMP-7. At the invasive front, MMP-7 has a vital role in carcinoma invasion, correlating with venous invasion of T1 CRCs.

The role of microvessel density, lymph node metastasis, and tumor size as prognostic factors of distant metastasis in colorectal cancer.

Angiogenesis is essential for tumor growth and metastasis. CD105 is reportedly a specific marker for tumor angiogenesis. It has been demonstrated that monoclonal antibodies to CD105 have high affinity for activated endothelial cells. A relationship between metastasis and microvessel density (MVD), as an indicator of neovascularization, has been identified in patients with colorectal cancer as shown by the presence of monoclonal antibodies to CD105. However, data on potentially confounding factors such as lymphatic and vascular infiltration and tumor size are lacking. We further investigated the relationship between MVD and distant metastasis, along with potentially confounding clinicopathological factors, to more precisely characterize this relationship. In this retrospective study, we analyzed colorectal cancer specimens surgically or endoscopically resected from January to September 2009. We defined MVD as the number of microvessels stained by monoclonal antibodies to CD105 per ×400 field. Selected clinicopathological factors were analyzed and stepwise multivariate logistic regression was performed to identify independent risk factors for distant metastasis. We analyzed 129 lesions. The median follow-up time was 34 months (range, 6-85 months) in patients with distant metastasis and 61 months (range, 60-86 months) in those without distant metastasis. At the time of resection or during subsequent follow-up, 32 patients had distant metastases. The MVD was significantly greater in patients with than without distant metastases (mean ± standard deviation: 10.4±4.9 vs. 7.6±3.3, P=0.008; Welch's t-test). Stepwise multivariate logistic regression indicated that MVD, regional lymph node metastasis, and tumor size were independent risk factors for distant metastases. Combining assessment of monoclonal antibodies to CD105-positive MVD with assessment of regional lymph node metastasis and tumor size may help to identify patients who need more intensive surveillance after surgery for colorectal cancer.

Expression of PTEN and its pseudogene PTENP1, and promoter methylation of PTEN in non-tumourous thymus and thymic tumours.

AIMS: Mutation or promoter methylation of the phosphatase tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN) promotes some cancers. Moreover, PTENP1 (PTEN pseudogene) transcript regulates PTEN expression and is thought to be associated with tumourigenesis in some cancers. Here, we investigated PTEN expression in thymic epithelium and thymic epithelial tumours. METHODS: Immunohistochemical analysis of PTEN was performed on two non-tumourous thymus (NT) samples, 33 thymomas (three type A, eight type AB, 11 type B1, six type B2, and five type B3), and four thymic carcinomas (TCs). In 16 cases (two NT, three A, five B1, two B2, one B3 and three TC), analyses of mutations, promoter methylation and comparisons of PTEN mRNA and PTENP1 transcripts were undertaken using PCR-direct sequencing, methylation-specific PCR, and reverse-transcription real-time PCR after target cell collection with laser microdissection. RESULTS: PTEN protein was not immunohistochemically detected in NT epithelium or types B1 or B2 thymoma cells, but was expressed in type A thymoma and carcinoma cells. Neither PTEN mutations nor promoter methylation were detected in any samples. Statistical analysis revealed that PTEN mRNA expression was highest in NT epithelium and lowest in type A thymoma cells. PTENP1 transcript expression did not significantly differ among NT, thymoma and TC samples. CONCLUSIONS: We speculated that NT epithelium and types B1/B2 thymoma cells have a mechanism of PTEN translation repression and/or acceleration of protein degradation, whereas type A thymoma cells exhibit transcriptional repression of PTEN mRNA and accelerated translation and/or protein accumulation.

Correlation between histological invasiveness and the computed tomography value in pure ground-glass nodules.

PURPOSE: The purpose of this study was to evaluate the correlation between histological invasiveness and the computed tomography (CT) value and size in pure ground-glass nodules (GGNs) to determine optimal "follow-up or resection" strategies. METHODS: Between 2001 and 2014, 78 resected, pure GGNs were retrospectively evaluated. The maximum diameter and CT value of pure GGNs were measured using a computer graphics support system. RESULTS: All GGNs with a maximum diameter ≤10 mm and CT value ≤-600 Hounsfield units (HU) were considered to be noninvasive lesions, while 21 of 26 (81 %) with a maximum diameter >10 mm and CT value >-600 HU were considered to be invasive lesions. With respect to the correlation between each histological type and pure GGN with a maximum diameter ≤10 mm and CT value ≤-600 HU, the specificity was 90 % and the sensitivity and negative predictive value were both 100 % in atypical adenomatous hyperplasia (AAH), while the specificity was 58 % and the sensitivity and positive predictive value were 0 % in minimally invasive and invasive adenocarcinoma. CONCLUSION: Pure GGNs with a maximum diameter of ≤10 mm and CT value of ≤-600 HU are nearly always pre-invasive lesions; therefore, surgery should be carefully selected in such patients.

Difference in distribution profiles between CD163+ tumor-associated macrophages and S100+ dendritic cells in thymic epithelial tumors.

BACKGROUND: In a number of human malignancies, tumor-associated macrophages (TAMs) are closely involved in tumor progression. On the other hand, dendritic cells (DCs) that infiltrate tumor tissues are involved in tumor suppression. However, there have been very few reports on the distribution profiles of TAMs and DCs in thymic epithelial tumors. We examined the difference in the distribution profiles between TAMs and DCs in thymoma and thymic carcinoma. METHODS: We examined 69 samples of surgically resected thymic epithelial tumors, namely, 16 thymic carcinomas and 53 thymomas, in which we immunohistochemically evaluated the presence of TAMs using CD68 and CD163 as markers and DCs using S100 as the marker in tumor tissue samples in comparison with normal thymic tissues. RESULTS: The percentage of samples with a large number of CD68+ TAMs was not significantly different between thymic carcinoma and thymoma (7/16 versus 16/53, p = 0.904). However, the percentage of sample with a large number of CD163+ TAMs was significantly higher in thymic carcinoma than in thymoma (15/16 versus 34/53, p = 0.024). In contrast, the percentage of samples with a large number of S100+ DCs was significantly lower in thymic carcinoma than in thymoma (2/16 versus 23/53, p = 0.021). CONCLUSIONS: To the best of our knowledge, we are the first to show a high percentage of CD163+ TAMs and a low percentage of S100+ DCs in thymic carcinoma samples, and our findings may provide an idea for future targeted therapeutic strategies for thymic carcinoma using antibodies that inhibit monocyte differentiation to TAMs, thereby skewing TAMs differentiation toward DCs. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_215.

Cyclin-dependent kinase inhibitors, p16 and p27, demonstrate different expression patterns in thymoma and thymic carcinoma.

OBJECTIVES: The role of cell cycle inhibitors in tumorigenesis has been proven in various neoplasms; however, their roles in thymic tumors are still unclear. We examined the expression of cell cycle inhibitors such as those of the Cip/Kip family (p21, p27, and p57) and the INK-4/ARF family (p16 and p14) in thymoma and thymic carcinoma. METHODS: Samples from 41 thymoma and 14 thymic carcinoma patients, and 34 normal thymic tissue samples were prepared for the study. Immunohistochemical analysis using antibodies to p21, p27, p57, p16, and p14 was carried out, and the positivity for these inhibitors in each group was estimated in terms of their subcellular location and percentage of cells showing positive staining. RESULTS: Nuclear p27 showed a stepwise decrease (p < 0.0001), and the cytoplasmic p27 showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. p16 in both the nucleus and cytoplasm showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. However, as for p21, p57, and p14, there was almost no nuclear or cytoplasmic expression in each group. CONCLUSIONS: Our findings suggest that low nuclear and high cytoplasmic p27 expression levels, and high nuclear and cytoplasmic p16 expression levels may correlate with the increase in thymic malignancy.

Mixed mucin-producing and squamous differentiated tumor of the uterine cervix: a report of a case as adenosquamous carcinoma in situ.

We report a non-invasive mixed mucin-producing and squamous differentiated tumor of the uterine cervix. This tumor was composed of two cell types: mucin-producing cells and non-mucin-producing cells. These cells were intimately mixed with each other, and showed intraepithelial spreading. The mucin-producing cells showed signet-ring or columnar shapes, and were localized to the lower-to-upper epithelial layer. The non-mucin-producing cells had eosinophilic cytoplasms with a monotonous appearance through the epithelium. Mitosis was sometimes observed in both cell types. Immunohistochemically, both cell types were positive for p16(INK4A) . The non-mucin-producing cells were positive for p63 and 34ßE12, suggesting squamous differentiation. Although most mucin-producing cells were p63(-) , a few of them were p63(+) and many 34ßE12 immunoreactive cells were found in the mucin-producing cells. This tumor was adenosquamous carcinoma in situ.

Immunohistochemical analysis of thymic carcinoma focusing on the possibility of molecular targeted and hormonal therapies.

OBJECTIVE: Thymic carcinoma is a rare mediastinal malignant tumor, and in many patients, the tumor is detected in an inoperable advanced stage. Even when chemotherapy is administered to such patients, the patients show a poor response. We investigated new biomarkers of therapeutic molecular targets. METHODS: This study included 44 patients diagnosed and treated for primary thymic epithelial tumors at Showa University Northern Yokohama Hospital, Showa University Hospital, and Showa University Fujigaoka Hospital from 2003 to 2011. We investigated new biomarkers of therapeutic molecular targets, such as the peroxisome proliferator-activated receptor γ (PPARγ), insulin-like growth factor 1 receptor (IGF1R), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), human epidermal growth factor type 2 (HER2)/neu, CD44, and L-type amino acid transporter 1 (LAT1), in thymic tumors. RESULT: Immunohistochemical analysis showed that the PPARγ positivity rate in thymic carcinoma was 32 %, which was significantly higher than that in thymoma (4 %). The IGF1R positivity rate in thymic carcinoma was 73 %, which was significantly higher than that in thymoma (27 %). CONCLUSION: Therefore, by examining the expressions of PPARγ and IGF1R, it would be possible to identify therapy-responsive patients and to improve results of thymic carcinoma treatment.

Autopsy cases of miliary tuberculosis: clinicopathologic features including background factors.

To assist physicians, especially young physicians, in identifying tuberculosis (TB) infection before the terminal stage, we analyzed 7 cases of numerous tuberculous granulomas in multiple organs and compared clinical and autopsy findings between cases. Patients ranged in age from 41 to 86 years at the time of death. The main chief complaint was fever of unknown origin (3 of 7 cases [43%]). The main underlying conditions were liver cirrhosis (2 of 7 cases [29%]) and chronic renal failure (2 of 7 cases [29%]). Two patients (29%) had been given methylprednisolone pulse therapy for various lung disorders. Active TB was not diagnosed before autopsy in 4 of 7 (57%) patients. Calcified lesions indicative of old TB were present in 4 of 7 (57%) patients. Thus, miliary tuberculosis may represent a re-emergence of latent TB infection in these cases. Various histologic features of nonreactive exudative inflammation were seen, along with granulomas containing Langhans giant cells with or without caseous necrosis in hypervascular organs, such as the lung, liver, and bone marrow. Physicians should be mindful of the possibility of miliary TB when older patients with hepatorenal disease and a history of TB infection have undergone immunosuppressive treatment. Active tuberculous infection can depend on the presence of an underlying disease and immunocompromise.

[A case of advanced colon cancer successfully treated with cetuximab diagnosed as EGFR-positive by liver biopsy].

Cetuximab, a monoclonal antibody used to target the epidermal growth factor receptor(EGFR), was approved for refractory and metastatic colon cancer expressing EGFR, and the EGFR expression must be confirmed. But the EGFR expression may become false negative by immunohistochemistry. When we used a past operation specimen for a search in particular, a correct evaluation may be difficult for prolonged formalin fixation. We report a case successfully treated by cetuximab, who was diagnosed as EGFR-negative by the past operation specimen, but as EGFR-positive by the liver biopsy specimen. A 51- year old woman with multiple organ metastases, who had experienced failure with prior oxaliplatin, irinotecan(CPT-11), 5- FU and bevacizumab regimens, was administered cetuximab plus CPT-11 because it was EGFR-positive by liver biopsy, and the tumor was obviously reduced. It is useful to obtain another specimen such as by liver biopsy, when the EGFR expression is negative by a past operation specimen.

High-grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: report of a case with cytomorphologic and immunocytologic analysis.

We report a case of high-grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round-to-short spindle shapes with round- to oval-shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar-shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α-sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h-caldesmon. Accordingly, when relatively monotonous round-to-short spindle tumor cells and taper-shaped tumor cells are observed in the female genital tract, high-grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high-grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation.

Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma.

We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.

[Cholangiocarcinoma with bile duct adenoma and hamartoma-like lesion in the bile duct].

A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.

Intraductal oncocytic papillary carcinoma of the pancreas showing numerous hyaline globules in the lumen.

Two cases of intraductal oncocytic papillary carcinoma (IOPC) treated surgically were analyzed on light microscopy and immunohistochemistry: that of a 61-year-old man and that of a 55-year-old man. There were no clinical symptoms in either case. Pancreatic abnormalities were discovered incidentally on CT. Various clinical examinations were carried out, and the preoperative diagnosis was intraductal papillary mucinous carcinoma (IPMC) in both cases. Surgery was performed. Macroscopic observation of tissue cross-sections indicated multilocular cystic mass containing polypoid lesions encapsulated by the dilated pancreatic duct. Histologically, the cyst walls were lined by columnar epithelial cells with complex papillary projections associated with oxyphilic cytoplasm, and they were strongly immunoreactive with anti-mitochondrial antibody in the cytoplasm. Electron microscopy showed numerous mitochondria in the cytoplasm. IOPC was diagnosed. Interestingly, amorphous hyaline globules were produced from the oxyphilic cells, which exhibited a bud-like appearance. The hyaline globules were not positive for mucin staining. No case of IPMC with hyaline globules has been reported to date. The production of hyaline globules may be related to oncocytic differentiation. It is suggested that hyaline globules should be regarded as a characteristic of IOPC.

Diffuse large B-cell lymphoma after transformation from low-grade follicular lymphoma: morphological, immunohistochemical, and FISH analyses.

Follicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma and frequently transforms to diffuse large B-cell lymphoma (DLBCL). To clarify some aspects of the natural history of FL, we retrospectively examined 43 consecutive patients who had DLBCL with pre- or coexisting FL grade 1 or 2. The patients comprised 22 men and 21 women with a median age of 53 years. Most of the patients (34/43) showed advanced-stage (III or IV) disease initially. We examined both FL and DLBCL components morphologically, immunohistochemically, and by interface fluorescence in situ hybridization (FISH: IGH/BCL2 fusion, BCL6 translocation) analysis. Most of the DLBCLs were classified as the centroblastic subtype, with two exceptions of the anaplastic subtype. Immunohistochemical analysis of both the FL and DLBCL components revealed the following respective positivity rates: CD20 100%/100%, CD10 86%/66%, Bcl-2 96%/91%, Bcl-6 84%/88%, MUM1 16%/34%, CD30 0%/20%, CD138 0%/0%, and CD5 0%/3%. Loss of CD10 (6/36, 17%) and gain of MUM1 (7/28, 25%) and CD30 (5/21, 24%) through transformation were not infrequent. High positivity rates for Bcl-2 and Bcl-6 were maintained throughout transformation. Among the DLBCLs, 84% were classified as the germinal center B-cell phenotype (GCB) and 16% as non-GCB in accordance with the criteria of Hans et al. IGH/BCL2 fusion was detected by FISH in 89% of FLs and 82% of DLBCLs. BCL6 translocation was detected in 1/6 (17%) DLBCLs without IGH/BCL2 fusion. Thus, although the morphological features and FISH results for DLBCL were consistent with transformed FL, the immunophenotype showed wide heterogeneity.

Case report of a focal nodular hyperplasia-like nodule present in cirrhotic liver.

An 81-year-old female was referred to Sapporo Medical University Hospital because of a nodular lesion 20 mm in diameter found in the liver S8 during follow-up for type C liver cirrhosis. Abdominal ultrasonography showed a capsule-like structure, and contrast computed tomography revealed hypervascularity at the early phase and inner pooling of the contrast medium with ring enhancement at the late phase. Magnetic resonance T2-weighted imaging (T2WI) demonstrated a hyperintensity nodule with further hyperintensity signals in some parts of the nodule, and the signal pattern differed from that of typical fibrosis. SPIO-magnetic resonance imaging showed partial hypointensity signals by T2WI, which indicated the presence of Kupffer cells. Angiography did not show a spoke-wheel pattern. The results by imaging modalities indicated that the nodule was atypical for hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH), and liver nodule biopsy was performed for histological diagnosis. Compared with the background liver, the nodule revealed high cellular density, cellular dysplasia at the periphery, a pseudo-crypt structure and irregular hepatic cord arrangement in some parts of the nodule. Among them, there was immature fibrous tissue containing arterioles with muscular hypertrophy. There has been no report of well-differentiated HCC with a central scar, and this case was presumed to be an FNH-like nodule with dysplasia physically associated with cirrhotic tissue.

Immunohistochemical expression of TTF-1 in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity.

The immunohistochemical expression of thyroid transcription factor-1 (TTF-1) was investigated in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity. Three groups were categorized according to cytological subtype: group A, adenocarcinomas with either a Clara cell and/or type II epithelial cell component (Clara/type II) or a mixed Clara/type II and bronchial surface epithelial cell component (BSE) (mCB), in addition to other components; group B, adenocarcinomas with components including either BSE, a goblet cell component (GOB) or a mixed BSE and GOB component (mBG), and lacking Clara/type II or mCB; group C, adenocarcinomas with only a poorly differentiated component (POR). In group A all Clara/type II, mCB, BSE and the majority of POR were TTF-1 positive. In group B the majority of BSE, POR and all GOB were TTF-1 negative. BSE and POR in both groups had a different phenotype, possibly reflecting their different natural history. In group C 80% of cases were TTF-1 positive, suggesting that the majority were derived from group A tumors.

The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma.

BACKGROUND: Nasal NK/T cell lymphoma is an aggressive disease and has a poor prognosis. Nasal NK/T cell lymphoma is refractory to conventional chemotherapy and has strong tendency of widespread relapse or dissemination into distant sites. METHODS: We immunohistochemically studied nasal NK/T-cell lymphoma to elucidate the unique characteristics of nasal NK/T-cell lymphoma, such as its higher metastatic tendency and its vast necrosis which leads to destruction of the involved tissues. The expression of P-glycoprotein and MMP-9 was evaluated in the 20 patients with nasal NK/T-cell lymphoma and 25 with nasal non-NK/T-cell lymphoma and the relationship between expression of these proteins and clinical results were analyzed in this report. RESULTS: Overall 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 51%, and 84%. Distant involvement free 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 53%, and 79%. Overall positivity for P-glycoprotein was observed in 10 of 19 patients with NTL and in 13 of 23 patients with non-NTL. When the overall survival rate was compared between patients with P-glycoprotein positive and negative, there was no difference between them. Sixteen of the 19 patients with nasal NK/T cell lymphoma expressed MMP-9. In contrast, only 8 of the 22 patients with nasal non-NK/T cell lymphoma expressed MMP-9. Distant involvement free 5-year survival rates for patients with MMP-9 negative, and MMP-9 positive were 92%, and 61%, respectively. The difference was statistically significant (p = 0.027). CONCLUSION: Positive immunoreactivity for P-glycoprotein was not an independent prognostic factor in nasal NK/T-cell lymphomas, which stresses the importance of exploring other mechanisms of drug resistance. The strong expression of MMP-9 is uniquely characteristic of nasal NK/T cell lymphoma and may contribute to its strong tendency to disseminatate and the extensive necrosis which is always seen. However, our results are based on univariate comparisons, and as such, should be viewed with some caution.

Favorable outcome in patients with breast cancer in the presence of pathological response after neoadjuvant endocrine therapy.

Neoadjuvant endocrine therapy (NAET) can expand the number of breast cancer patients who can be treated with breast-conserving surgery and can predict benefit from adjuvant endocrine therapy. Because no validated surrogate markers for long-term outcome have been established, we conducted prospective trials to evaluate pathological response and Ki-67 index following treatment with tamoxifen or anastrozole. The study population included postmenopausal women with operable breast tumors that were both estrogen and progesterone receptor-positive and larger than 3 cm. Response was classified as pathological response (minimal response or better) and non-response. Non-responding (25.5%, vs. response 85.9%, p=0.002), axillary node-positive (58.4% vs. node negative 100%, p=0.045), and high pretreatment Ki-67 index (41.4% vs. low Ki-67 87.1%, p=0.03) patients were significantly associated with poor 5-year relapse-free survival. Multivariate analysis of relapse-free survival indicated that pathological response was independent. Therefore, pathological response may be a favorable prognostic factor after NAET.