Clinicopathological and Molecular Analysis of 45 Cases of Pure Mucinous Breast Cancer.

Pure mucinous breast carcinoma (PMBC) is characterized by clusters of tumor cells floating in abundant extracellular mucin and can be classified into paucicellular (Type A) and hypercellular (Type B) subtypes. However, the clinicopathological and genomic differences between these two subtypes have not been well characterized. We retrospectively investigated the clinicopathologic features of 45 cases of surgically removed PMBC (31 Type A and 14 Type B). We also performed whole-exome sequencing (WES) in eight cases of PMBC. We found that Type B PMBC occurs at an older age and shows more aggressive clinical behavior than Type A. WES analysis revealed that HYDIN was the most frequently mutated gene in both types of PMBC. Although Type B PMBC showed a tendency toward more frequent genetic alterations, there were no statistically significant differences between the two subtypes in single nucleotide variants or insertions or deletions of bases associated with moderate or high effects. Our results provide additional evidence that PMBCs are clinicopathologically and genetically heterogeneous and lack pathognomonic genetic alterations. Further, Type B PMBC is more frequently associated with lymph node metastasis than Type A.

Comparison of neoadjuvant adriamycin and docetaxel versus adriamycin, cyclophosphamide followed by paclitaxel in patients with operable breast cancer.

PURPOSE: Neoadjuvant chemotherapy is the standard treatment for patients with locally advanced breast cancer and is increasingly considered for patients with operable disease. Recently, as many clinical trials have demonstrated favorable outcomes of anthracycline-taxane based regimen, this approach has been widely used in the neoadjuvant setting. METHODS: We compared women who received adriamycine and docetaxel (AD) with adriamycin, cyclophosphamide followed by paclitaxel (AC-T) as neoadjuvant chemotherapy. The AD group was scheduled for six cycles of AD (50 mg/m(2) and 75 mg/m(2), respectively) at a 3-week interval. The AC-T group was scheduled for four cycles of adriamycin and cyclophosphamide (50 mg/m(2) and 500 mg/m(2), respectively) followed by four cycles of paclitaxel (175 mg/m(2)) at a 3-week interval. RESULTS: The responses of chemotherapy were equivalent (overall response rate [AD, 75.7% vs. AC-T, 80.9%; P = 0.566], pathologic complete response [pCR] rate [breast and axilla: AD, 10.8% vs. AC-T, 12.8%; P = 1.000; breast only: AD, 18.9% vs. AC-T, 14.9%, P = 0.623], breast conserving surgery rate [P = 0.487], and breast conserving surgery conversion rate [P = 0.562]). The pCR rate in the breast was higher in the human epidermal growth factor receptor 2 (HER2) positive cases (HER2 positive 33.3% vs. negative 10%, P = 0.002). Although nonhematologic toxicities were comparable, hematologic toxicities were more severe in the AD group. Most women in the AD group suffered from grade 3/4 neutropenia (P < 0.001) and neutropenic fever (P < 0.001). CONCLUSION: Tumor responses were not different in various variables between the two groups. However, AC-T was a more tolerable regimen than AD in patients with breast cancer receiving neoadjuvant chemotherapy.

Granulocytic sarcoma in breast after bone marrow transplantation.

Granulocytic sarcoma is a localized extramedullary solid tumor composed of immature myeloid cell and is usually associated with acute myeloid leukemia or myelodysplastic syndrome. Although it can involve any site, commonly in lymph nodes, skin, bone and soft tissue, the involvement of breast is unusual. Especially, the involvement of the breast as a pattern of relapse after bone marrow transplantation is extremely rare. We have experienced 2 cases of granulocytic sarcoma after bone marrow transplantation. One case was a 39-year-old woman with right breast mass diagnosed with granulocytic sarcoma. She had received an unrelated bone marrow transplantation due to biphenotype acute leukemia 3 years before our presentation. Another case was a 48-year-old woman with acute myeloid leukemia, who was diagnosed with granulocytic sarcoma on both breasts 8 months after allogenic bone marrow transplantation. We also discuss the clinicopathologic features of granulocytic sarcoma in breast after bone marrow transplantation.

Differential diagnosis in idiopathic granulomatous mastitis and tuberculous mastitis.

PURPOSE: Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of unknown etiology. The diagnosis of IGM requires that other granulomatous lesions in the breast be excluded. Tuberculous mastitis (TM) is also an uncommon disease that is often difficult to differentiate from IGM. The purpose of this study is to develop a new algorithm for the differential diagnosis and treatment of IGM and TM. METHODS: Medical records of 68 patients (58 with IGM and 10 with TM) between July 1999 and February 2009 were retrospectively reviewed. RESULTS: The mean age of the patients was 33.5 (IGM) and 40 (TM) years (p=0.018). The median follow-up was 84 months. Of the total 10 patients with TM, 5 patients had a history of pulmonary tuberculosis. The most common symptoms of the diseases were breast lump and pain. However, axillary lymphadenopathy was more seen in TM (50%) compared to IGM (20.6%) (p=0.048). TM showed more cancer-mimicking findings on radiologic study (p=0.028). In IGM, 48 patients (82.7%) underwent surgical wide excision and 21 patients (36.2%) were managed with corticosteroid therapy and antibiotics. All of the TM patients received anti-tuberculosis medications and 9 patients (90%) underwent wide excision. The mean treatment duration was 2.8 months in IGM and 8.4 months in TM. Recurrence developed in 5 patients (8.6%) in IGM and 1 patient (10%) in TM. CONCLUSION: This study shows different characteristics between IGM and TM. The IGM patients were younger and had more mastalgia symptoms than the TM patients. Axillary lymphadenopathy was seen more often in TM patients. Half of the TM patients had pulmonary tuberculosis or tuberculosis lymphadenitis. Surgical wide excision might be both therapeutic and useful for providing an exact diagnosis.

Role of corticotrophin-releasing factor in the stress-induced dilation of esophageal intercellular spaces.

Corticotrophin-releasing factor (CRF) plays a major role in coordinating stress responses. We aimed to test whether blocking endogenous CRF activity can prevent the stress-induced dilation of intercellular spaces in esophageal mucosa. Eighteen adult male rats were divided into 3 groups: 1) a non-stressed group (the non-stressed group), 2) a saline-pretreated stressed group (the stressed group), 3) and an astressin-pretreated stressed group (the astressin group). Immediately after completing the experiments according to the protocol, distal esophageal segments were obtained. Intercellular space diameters of esophageal mucosa were measured by transmission electron microscopy. Blood was sampled for the measurement of plasma cortisol levels. Mucosal intercellular spaces were significantly greater in the stressed group than in the non-stressed group. Mucosal intercellular spaces of the astressin group were significantly smaller than those of the stressed group. Plasma cortisol levels in the stressed group were significantly higher than in the non-stressed group. Pretreatment with astressin tended to decrease plasma cortisol levels. Acute stress in rats enlarges esophageal intercellular spaces, and this stress-induced alteration appears to be mediated by CRF. Our results suggest that CRF may play a role in the pathophysiology of reflux-induced symptoms or mucosal damage.

An antinuclear antibody-negative patient with lupus nephritis.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease that's characterized by various autoantibodies to nuclear and cytoplasmic antigens. The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of SLE. However, a small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative ANA tests. Our report describes a 16-yr-old female who presented with the clinical manifestations of SLE such as malar rash, photosensitivity, arthritis, lymphopenia, pericarditis and proteinuria. The serum autoantibodies were all negative and renal biopsy showed that the histopathological changes of immune complex mediated the focal segmental necrotizing glomerulonephritis with crescent formation. She was treated with monthly pulse cyclophosphamide along with corticosteroids. During the 2-yr follow-up period, the proteinuria was markedly decreased and all of the ANA and anti-double stranded DNA antibody tests were negative. This case suggests that ANA may not be required in the pathogenesis of lupus nephritis.

Histamine release and inflammatory cell infiltration in airway Mucosa in methylene diphenyl diisocyanate (MDI)-induced occupational asthma.

INTRODUCTION: Although methylene diphenyl diisocyanate (MDI) is widely used in industries, there have been few studies of the pathogenic mechanisms of MDI-induced occupational asthma (MDI-OA). METHODS: We performed immunohistochemical analyses, measured inflammatory mediators and cytokines, and quantified histamine release (HR) from peripheral basophils in MDI-OA patients. Thirteen MDI-exposed workers (five MDI-OA, two MDI-induced esoinophilic bronchitis, and six asymptomatic exposed controls, AEC) were enrolled. RESULTS AND DISCUSSION: Immunochemical analyses indicated significantly increased anti-eosinophilic cationic protein-stained cells in MDI-OA patients as compared with controls (P < 0.05). Sputum eosinophil cationic protein levels were increased after MDI-specific inhalation challenge test in MDI-OA/EB patients (P < 0.02). Sputum eosinophil counts were highly correlated with IL-8 and MMP-9 levels (P < 0.05 and P < 0.01, respectively). Basophil HR was significantly increased in MDI-OA patients after stimulations with anti-IgG4 and MDI-human serum albumin conjugates (both P < 0.05). Eosinophil activation is a major feature of airway inflammation in MDI-OA patients. Increased HR by MDI may contribute to the pathogenic mechanisms of MDI-OA.

Clinical significance of bone marrow micrometastasis detected by nested rt-PCR for keratin-19 in breast cancer patients.

PURPOSE: Breast cancers in the early phase frequently undergo distant metastasis and survival of patients is greatly dependent on distant metastasis. The occurrence of micrometastasis has been suggested to relate with prognostic features of breast cancer, such as lymph node metastasis and the presence of vascular invasion. The aim of this study was to examine the presence of keratin-19 mRNA of epithelial tumors in bone marrow aspirates obtained from breast cancer patients and its possible correlation with tumor staging and disease-free survival. METHODS: Bone marrow samples were obtained from 59 breast cancer patients at the time of surgery. We separated the mononuclear fraction from the samples and carried out nested reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of keratin-19 mRNA with two different pairs of primers. After operation, the patients were followed up at 3-month intervals. We studied the possible correlation of the detection of keratin-19 mRNA with tumor size, nodal involvement, stage and recurrence rate. RESULTS: Bone marrow micrometastasis was detected by nested RT-PCR for keratin-19 mRNA in one of four patients with ductal carcinoma in situ (DCIS), 13 of 30 patients with T1, 11 of 20 patients with T2 and all four patients with T3 lesion. Recurrence was observed in seven cases and all of them were positive for micrometastasis in bone marrow. CONCLUSION: The method of nested RT-PCR to detect the presence of keratin-19 mRNA in bone marrow from patients with breast cancer is sensitive and reliable. Moreover, early recurrence was observed in the patients with the tumor mRNA detected in bone marrow. Additional studies with larger numbers of patients and longer follow-up are desirable.