Idiopathic granulomatous mastitis: a 25-year experience

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory condition of the breast that can mimic inflammatory breast cancer and periductal mastitis (PDM). Eighteen patients with a histopathologic diagnosis of IGM, seen over a period of 25 years, were retrospectively reviewed and compared with 133 patients with PDM and 100 normal patients. STUDY DESIGN: The unit's pathology database and clinic letters for this time period were used to identify patients who had presented with IGM. A retrospective review of the notes was used to extract reproductive factors, cigarette smoking habits, and ethnicities that were recorded at presentation. These were compared with data from a similar group of patients with PDM and a control group. RESULTS: All IGM patients were women. Median age was 36 years (range 18 to 67 years) compared with 52 years (range 20 to 77 years) for PDM patients (p < 0.001). Seventeen percent of IGM patients were smokers at the time of presentation, as compared with 60% of PDM patients (p < 0.001). Although parity was similar for all groups, 10 IGM patients (56%) had given birth in the last 5 years, compared with 6 (5%) PDM patients (p < 0.001) and 20 (20%) in the control group (p=0.0194). Two IGM patients had recurrences after pregnancy. The course of IGM varied from 11 to 105 weeks and was not affected by any treatment modalities. CONCLUSIONS: IGM patients are younger, have given birth more recently, and are less likely to be Caucasian as compared with PDM patients. IGM is not related to smoking and can recur. Treatment should be supportive.     

To switch or not to switch: should the updated Intergroup Exemestane Study alter our decision?

Adjuvant therapy for breast cancer with aromatase inhibitors improves survival compared with tamoxifen; however, whether they should be given upfront or sequentially after 2-3 years of tamoxifen in estrogen receptor-positive early breast cancer affecting postmenopausal women is unclear. The Intergroup Exemestane Study looked at 4724 postmenopausal patients with estrogen receptor-positive or unknown breast cancer who had been disease free for 2-3 years on tamoxifen and were randomly assigned to switch to exemestane or to continue tamoxifen for the remainder of a 5-year endocrine treatment period. A significant disease-free survival advantage (p = 0.0001) was seen in favor of exemestane, with an absolute benefit of 3.3% by the end of treatment. This trial is the first to show an overall survival advantage for switching in estrogen receptor-positive breast cancer (p相似文献   

A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease

Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.Key words: Early-onset Pompe disease, Acid maltase deficiency, Founder effectGlycogen storage disease type II (Online Mendelian Inheritance in Man, OMIM, accession number 232300), also called Pompe disease, was described by Johannes C. Pompe in 1932. The disorder is caused by a deficiency of the enzyme acid alpha-glucosidase (acid maltase, EC 3.2.1.20, Swiss) which originates lysosomal glycogen accumulation leading to lysosomal swelling, cellular damage and dysfunction (1-3). Affected individuals develop progressive neuromuscular damage, showing a debilitating and frequently fulminating course on the classical, early-onset type of the disease. Other main findings are hypertrophic cardiomyopathy, hypotonia, hepatomegaly, macroglossia, feeding problems and breath difficulty. Currently it is recognized that the late form of Pompe disease has a very variable phenotype that can be confused with a wide range of neuromuscular, pulmonary and cardiovascular diseases with mild, moderate or severe symptoms that present either alone or combined (4-6).Pompe disease has an autosomal recessive inheritance and it is caused by more than 300 mutations that occur all over the gene coding for acid alpha-glucosidase (GAA) located at locus 17q25.2q25.3. The molecular phenomenon responsible of the different types of clinical expression occur by the presence of two either homozygous or compound heterozygous pathogenic mutations in early-onset Pompe cases, whereas late-onset Pompe have one variant and one pathogenic mutation (7). The majority of disease-causing mutations are unique; nonetheless, relatively frequent mutations have been described in certain populations with a possible founder effect traced from the original mutated carrier to the newly occurring cases. Affected cases have been described worldwide with a few high-prevalence regions like South-Africa, Taiwan and Holland (1, 8-10).Herein, we described two unrelated cases affected with classical early-onset Pompe disease, both pertaining to the same small Mexican region, with the same novel homozygous frameshift mutation at gene GAA (c.1987delC), identified by complete gene sequencing.     

Impact of full-field digital mammography on pre-operative diagnosis and surgical treatment of mammographic microcalcification

Accurate pre-operative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification (MM) as ductal carcinoma in situ (DCIS) or invasive breast cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44 % of cases. Despite correct pre-operative diagnosis of MM, 26 % require second therapeutic operations to achieve surgical clearance. Theoretically, improved conspicuity of malignant MM using digital mammography could improve diagnostic work-up and improve surgical outcomes for MM. To determine the impact of full-field digital mammography (FFDM) on the diagnostic accuracy and positive predictive value (PPV) of biopsy of MM and surgical management of MM, screening and symptomatic cases with MM (n = 1,479) were reviewed for women imaged between August 2007 and March 2010 using screen-film mammography (SFM) (n = 711), and using FFDM, imaged between April 2010 to March 2012 (n = 768). Demographic information including pre and postoperative diagnosis, and number and types of surgical procedures were recorded. Overall, 302 (128 invasive) and 251 (110 invasive) malignant lesions were diagnosed using SFM and FFDM, respectively. Reduction in PPV of biopsy was observed (SFM 42.5 %; FFDM 32.7 %, p < 0.001). Correct pre-operative diagnosis was achieved at first attempt more often with FFDM (SFM 80.6 %; FFDM 89.5 %, p < 0.001). For lesions with pre-operative diagnosis, B5 more cases achieved surgical clearance with a single therapeutic operation with FFDM (SFM 66.3 %; FFDM 76.7 %, p = 0.017), and more lesions over 2 cm underwent mastectomy as the initial surgical procedure (SFM 47.0 %; FFDM 62.9 %, p = 0.005). Correct pre-operative diagnosis of MM using digital mammography reduced second therapeutic operations but increased mastectomy rate in larger cancers over two centimetres. This will increase concerns about treatment of lesions detected in the screening programme with widespread use of digital mammography.     

Model of normal prepubertal growth

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was 'regular' were directly marked on single night records. Sleep state was determined from respiratory variables. 'Regular' breathing was a reliable marker of 'quiet' sleep (specificity 93%). The duration of 'quiet' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.     

Comparison of IgG subclasses in foetal serum, maternal serum at delivery and milk in IgA-deficient and control women

Immunoglobulin G subclass concentrations were measured in paired foetal (cord) and maternal serum specimens at delivery from 27 IgA-deficient (serum IgA < 0.01 g/l) and 15 control women. IgA-deficient women had significantly higher serum IgGl and IgG3 concentrations than control women but 2 of the group had concomitant IgG2/IgG4 deficiency and a further 12 had low IgG4 concentrations (serum IgG4 < 0.025 g/l). Foetal serum also had significantly higher IgGl concentrations than control foetal serum but lower IgG2 and IgG4 levels. Concentrations of IgG subclasses and IgM were measured in breast milk collected on the fifth day postpartum from 19 of these IgA-deficient and 18 control women. Between-group differences in IgG subclass levels resembled those in serum. Compared with serum, proportionally less IgG3 was present in milk in both groups although the contribution of IgG3 to total IgG was not less than that of IgG4. Slightly higher IgM was found in milk from the IgA-deficient mothers.     

Adult height in patients with childhood onset atopic dermatitis

Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible.     

The importance of complete excision in the prevention of local recurrence of ductal carcinoma in situ.

Mastectomy probably represents over-treatment for the majority of women with screen detected ductal carcinoma in situ (DCIS) and breast-conserving surgery is now widely advocated. In this study, biopsy cavity shavings were used to ensure complete excision in 129 women undergoing breast-conserving surgery for screen detected DCIS. A margin was considered clear if DCIS was > 1 mm from any margin of excision and shavings were clear. Patients with involved margins (DCIS at resection margin) underwent re-excision, irrespective of shaving status. After re-excision, 101 women (78%) had clear margins and 28 (22%) close margins (DCIS < or = 1 mm from resection margin). Cavity shavings were histologically clear of DCIS in all cases. Ipsilateral DCIS recurrence occurred in 12 (9.3%) patients. Two recurrences also contained invasive carcinoma. The median time to diagnosis was 14 months and all recurrences occurred at the site of the previous biopsy. Seven recurrences were detected at the first annual mammogram, four at the second and one at the third. Ipsilateral recurrence was related to margin status; only 2 out of 101 (2%) patients with clear margins recurred, compared with 10 out of 28 (36%) patients with close margins. Local recurrence and close margin status both correlated with a high modified Van Nuys prognostic index score. Our results indicate that local relapse represents residual DCIS rather than true recurrence in the majority of cases. Cavity shavings have proved ineffective in ensuring complete excision. We now ensure a minimum 10 mm margin of excision around all screen-detected DCIS lesions.     

Studies of epidermal growth factor receptor inhibition in breast cancer

Until recently, there has been little knowledge on the growth control of oestrogen receptor (ER)-negative ductal carcinoma in situ (DCIS) and invasive breast cancer. The recent development of DCIS models, such as transgenic mice, cell-line xenograft models and, importantly, in vivo human DCIS xenograft models has facilitated the investigation and understanding of the control of growth of early pre-invasive breast lesions. Recent studies have shown that ER-negative DCIS, unlike ER-positive DCIS, is hormone independent and does not respond to anti-oestrogen treatment. Moreover, DCIS of the comedo type utilises type I tyrosine kinase growth factors, such as epidermal growth factor receptor (EGFR) and c-erbB-2, in receptor signalling for growth. New data underscore the importance of EGFR as the major modulating growth factor receptor in the control of proliferation in the breast. Pre-clinical studies performed on human DCIS xenografts in nude mice suggest a potential role for EGFR tyrosine kinase inhibitors (EGFR-TKIs). More specifically, ZD1839, a novel orally active and selective EGFR-TKI, has been shown to produce a response in DCIS through a decrease in epithelial proliferation. These findings have enhanced our knowledge of signal transduction pathways in cancer and indicate that tyrosine kinase blockade of EGFR has potential for the treatment and chemoprevention of DCIS. It is hoped that further advances in this area and evaluation of EGFR-TKIs in Phase II/III clinical trials will allow their therapeutic potential as anticancer agents to be appreciated.