Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ

BACKGROUND Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Proliferation index in ductal carcinoma in situ of the breast: Relation to estrogen, progesterone and HER2/neu receptors

Background. Ductal carcinoma in situ (DCIS) is the most prevalent precursor to invasive breast cancer (IBC), the second leading cause of death in women in the United States. The three most important prognostic markers for IBC are Estrogen receptor (ER), Progesterone receptor (PR) and HER2/neu. The four groups (IBC) defined as (1) ER and/or PR positive and HER2/neu negative, (2) ER and/or PR positive and HER2/neu positive (3) ER and/or PR negative and HER2/neu positive and (4) negative for all three of these receptors (Triple negative). However, they have not been well studied in DCIS. This is an exploratory study with a primary objective to examine the prevalence of ER, PR, and HER2/neu in DCIS, to explore if the defined groups of IBC occur in DCIS and to consider the biological relationship between these four groups and the proliferative activity of the tumor. A secondary goal of this study is to examine the relationship between grade and proliferative activity. Methods. Using immunohistochemistry, I have measured Ki-67, ER, PR and HER2/neu positivity for a series of cases of DCIS. Results. 20 ER and/or PR positive and HER2/neu negative (50%) with average PI of 0.05, 7 ER and/or PR positive and HER2/neu positive (17.5%) with average PI of 0.14, 10 ER and/or PR negative and HER2/neu positive (25%) with average PI of 0.18, and three triple negative (7.5%) with average PI of 0.18. ER and/or PR positive and HER2/neu positive group has the highest PI (p<0.001). Further, the ER and/or PR positive and HER2/neu positive group show a linear relationship between PI and average ER/PR positivity (R=0.6). PI increases with higher grades. Conclusion. PI appears to depend upon the average fraction of positive ER/PR tumor cells, possibly with a synergistic dependence when HER2/neu is positive. If ER/PR is negative, then both HER2/neu positive and the triple negative cases appear to cluster around an average PI that is higher than the average PI in HER2/neu negative ER/PR positive negative cases. In the triple negative tumors there must be another driver of proliferation.^

Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast

Aims: Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC. Methods and results: A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002). Conclusions: Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.

The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)?

Lobular carcinoma in situ was first described over 60 years ago. Despite the long history, it continues to pose significant difficulties in screening, diagnosis, management and treatment. This is partly due its multi-focal and bilateral presentation, an incomplete understanding of its biology and natural history and perpetuation of misconceptions gathered over the last decades. In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion. (c) 2006 Elsevier Ltd. All rights reserved.

Pancreatic large mucinous cystoadenoma with invasive ductal carcinoma in pregnancy. Case report

Background. Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy. Case report. A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors. Conclusions. To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.

Efficacy and Safety of Using Amplatzer Ductal Occluder for Transcatheter Closure of Perimembranous Ventricular Septal Defect in Pediatrics

Background: Perimembranous Ventricular Septal Defect (PMVSD) is the most common subtype of ventricular septal defects. Transcatheter closure of PMVSD is a challenging procedure in management of moderate or large defects. Objectives: The purpose of this study was to show that transcatheter closure of perimembranous ventricular septal defect with Amplatzer Ductal Occluder (ADO) is an effective and safe method. Patients and Methods: Between April 2012 and April 2013, 28 patients underwent percutaneous closure of PMVSD using ADO. After obtaining the size of VSD from the ventriculogram a device at least 2 mm larger than the narrowest diameter of VSD at right ventricular side was chosen. The device deployed after confirmation of its good position by echocardiography and left ventriculography. Follow up evaluations were done 1 month, 6 months, 12 months and yearly after discharge with transthoracic echocardiography and 12 lead electrocardiography. Results: The mean age of patients at procedure was 4.7 ± 6.3 (range 2 to 14) years, mean weight 14.7 ± 10.5 (range 10 to 40) kg. The mean defect size of the right ventricular side was 4.5 ± 1.6 mm. The average device size used was 7.3 ± 3.2mm (range 4 to 12 mm). The ADOs were successfully implanted in all patients. The VSD occlusion rate was 65.7% at completion of the procedure, rising up to 79.5% at discharge and 96.4% during follow-up. Small residual shunts were seen at completion of the procedure, but they disappeared during follow-up in all but one patient. The mean follow-up period was 8.3 ± 3.6 months (range 1 to 18 months). Complete atrioventricular block (CAVB), major complication or death was not observed in our study. Conclusions: Transcatheter closure of PMVSD with ADO in children is a safe and effective treatment associated with excellent success and closure rates, but long-term follow-up in a large number of patients would be warranted.

Hepatic Involvement In Paediatric Patients With Paracoccidioidomycosis: A Histological Study.

Paracoccidioidomycosis is a systemic mycosis that is endemic to certain countries in Latin America. This study aimed to describe the histological features of liver involvement in patients with paracoccidioidomycosis aged <16 years of age who were treated between 1980 and 2010, with a diagnosis that was confirmed by detection of the fungus by pathological examination. Liver tissue was obtained from one necropsy and 12 biopsies. Throughout 2007, biopsies were taken from patients with persistent jaundice or portal hypertension, after which biopsies became indicated due to elevated aminotransferase and low albumin levels. Using haematoxylin and eosin (H&E), Masson's trichrome and immunohistochemical (CK7 and CK19) staining, we noted degenerative alterations in bile duct cells and inflammatory injury to the bile ducts in 10 biopsies. Using immunohistochemistry for CK7 and CK19, we observed ductal proliferation in all 12 samples. Bile duct injuries by inflammatory cells might explain the predominant increase in canalicular enzymes; immunohistochemistry is more sensitive in demonstrating ductular reactions and might show changes that are not apparent on H&E staining.

Intraductal Carcinoma Of The Prostate: Interobserver Reproducibility Survey Of 39 Urologic Pathologists.

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.

Tubular Variant Of Basal Cell Adenoma Shares Immunophenotypical Features With Normal Intercalated Ducts And Is Closely Related To Intercalated Duct Lesions Of Salivary Gland.

The morphological criteria for identification of intercalated duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20-70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (<5%). One patient presented IDLs, tubular BCAs and IDL/tubular BCA combined lesions. Luminal ductal cells of IDLs and tubular BCAs exhibited positivity for CK7, lysozyme, S100 and DOG1. In the non-tubular BCA group, few luminal cells exhibited such an immunoprofile; they were mainly CK14-positive. Basal/myoepithelial cells of IDLs, tubular BCAs and non-tubular BCAs were positive for CK14, calponin, α-SMA and p63; they were more numerous in BCA lesions. IDL, tubular BCA and non-tubular BCA form a continuum of lesions in which IDLs are related closely to tubular BCA. In both, the immunoprofile of luminal and myoepithelial cells recapitulates the normal intercalated duct. The difference between the adenoma-like subset of IDLs and tubular BCA rests mainly on the larger numbers of myoepithelial cells in the latter. Our findings indicate that at least some BCAs can arise via IDLs.

Structural aspects of the p.P222Q homozygous mutation of HSD3B2 gene in a patient with congenital adrenal hyperplasia

Type II 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD2), encoded by the HSD3B2 gene, is a key enzyme involved in the biosynthesis of all the classes of steroid hormones. Deleterious mutations in the HSD3B2 gene cause the classical deficiency of 3β-HSD2, which is a rare autosomal recessive disease that leads to congenital adrenal hyperplasia (CAH). CAH is the most frequent cause of ambiguous genitalia and adrenal insufficiency in newborn infants with variable degrees of salt losing. Here we report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child, who was born from consanguineous parents, and presented with ambiguous genitalia and salt losing. The patient carries a homozygous nucleotide c.665C>A change in exon 4 that putatively substitutes the proline at codon 222 for glutamine. Molecular homology modeling of normal and mutant 3β-HSD2 enzymes emphasizes codon 222 as an important residue for the folding pattern of the enzyme and validates a suitable model for analysis of new mutations.

Metabolic evaluation of young women with congenital adrenal hyperplasia

OBJECTIVE: To evaluate insulin resistance and lipid profile in women with congenital adrenal hyperplasia (CAH) caused by classical 21-hydroxylase deficiency (21OHD), and their association with body mass index (BMI) and corticosteroid dosage. SUBJECTS AND METHODS: We assessed BMI, waist circumference, current glucocorticoid dosage, glucose, insulin and lipid profile in eighteen young women (mean ± SD, 19.3 ± 3.0 years) with 21OHD CAH. RESULTS: BMI was normal in 12 patients, 5 of them were overweight, and 1 was obese. Waist circumference was high in 7 patients. Fasting insulin and HOMA-IR were elevated in seven and eight patients, respectively. Total cholesterol and triglycerides were high in only two patients, and HDL-cholesterol was low in four. Insulin resistance was not associated with BMI, waist circumference or glucocorticoid dose. CONCLUSIONS: Young women with 21OHD CAH had infrequent dyslipidemia, but had a higher prevalence of insulin resistance and central obesity, that were independent of BMI or corticosteroid dosage.

46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively. Arq Bras Endocrinol Metab. 2012;56(8):578-85

Lipoidoproteinose

OBJETIVO: Apresentar as características clínicas, tratamento cirúrgico e achado histológico de um caso de lipoidoproteinose. DESCRIÇÃO DO CASO: Criança do sexo masculino, cinco anos de idade, branco, que procurou atendimento odontológico na Universidade. A mãe da criança relatou presença de intensa halitose e dificuldade na alimentação e higienização bucal, decorrentes de crescimento gengival generalizado nos arcos dentários superior e inferior. No exame clínico, verificaram-se comprometimento funcional e estético generalizado (rouquidão, artralgia bilateral no joelho e tornozelo, lesões tumorais nas orelhas, entre outros), além de extensa hiperplasia gengival em ambos os arcos dentários. Optou-se pelo tratamento cirúrgico, com remoção do tecido hiperplásico e exodontia de todos os dentes decíduos e de dois permanentes. O exame histopatológico da peça cirúrgica confirmou o diagnóstico de lipoidoproteinose. COMENTÁRIOS: A lipoidoproteinose é uma doença rara caracterizada pela deposição da substância hialina na pele, membranas mucosas e nos órgãos internos. Os sinais que podem surgir após o nascimento, são: rouquidão; lesões pápulo-nodulares na cabeça, pescoço e membros; lesões papulares amareladas nas margens das pálpebras. O curso desta doença é benigno e crônico.

Processos proliferativos gengivais não neoplásicos em paciente sob tratamento ortodôntico

INTRODUÇÃO: a aparatologia ortodôntica dificulta a higiene bucal e pode contribuir para a formação de lesões gengivais, como os processos proliferativos gengivais não neoplásicos. Essas lesões, dependendo de alguns fatores - como o tempo de evolução, constituintes histopatológicos e condições bucais -, podem ser reversíveis, em alguns casos, por meio da orientação sobre higiene bucal e da terapia periodontal básica. Entretanto, na maioria das vezes há necessidade de tratamento cirúrgico. OBJETIVO: o propósito deste trabalho é relatar o caso de uma paciente portadora de aparatologia ortodôntica fixa que apresentou duas lesões gengivais distintas, diagnosticadas como granuloma piogênico e hiperplasia gengival inflamatória. Foram discutidas as características clínicas e histopatológicas, incidência e frequência, modalidades terapêuticas e prevenção de ambas as lesões, demonstrando a importância do encaminhamento do material colhido ao exame histopatológico, dada a possibilidade de diversas hipóteses diagnósticas. Em ambas as lesões foi realizada a exérese cirúrgica. RESULTADOS: a lesão na arcada superior, diagnosticada como granuloma piogênico, apresentou recorrência, sendo necessária terapia periodontal básicae repetiçãodoprocedimento cirúrgico. Alesão na arcada inferior foi diagnosticada como hiperplasia gengival, sendo removida cirurgicamente e acompanhada clinicamente, com prescrição de orientação da higiene bucal ao paciente