Granulomatous mastitis caused by Rickettsia species.

Granulomatous mastitis is a rare inflammatory disease of varying etiology. Tuberculosis and cystic neutrophilic granulomatous mastitis caused by Corynebacterium are the best-established infectious examples. Despite the increasing incidence of Rickettsia-related diseases worldwide, granulomatous inflammation of breast parenchyma caused by Rickettsia has not yet been reported. We present a unique case of bilateral granulomatous mastitis documented with mammography, magnetic resonance imaging and core-needle biopsy. The rickettsial etiology of the disease was proved with specific immunohistochemistry and confirmed with DNA extraction, PCR and serology. The lesions completely resolved after a full-course tetracycline treatment. This case report widens the knowledge about the possible clinical manifestations of Rickettsia infection and adds a new bacterium to the list of etiological factors causing granulomatous mastitis.

The clinical value of detecting microcalcifications on a mammogram.

Many breast lesions are associated with microcalcifications that are detectable by mammography. In most cases, radiologists are able to distinguish calcifications usually associated with benign diseases from those associated with malignancy. In addition to their value in the early detection of breast carcinoma and accurate radiological diagnosis, the presence of microcalcifications often affects the extent of surgical intervention. Certain types of microcalcifications are associated with negative genetic and molecular characteristics of the tumor and unfavorable prognosis. Microcalcifications localized in the larger ducts (duct-centric, casting-type microcalcifications) represent an independent negative prognostic marker compared to lesions containing other types of microcalcifications and to non-calcified lesions. In this review, we summarize the theoretical and methodological background for understanding the clinical impact and discuss the diagnostic and prognostic value of microcalcifications detected in the breast by mammography.

The subgross morphology of breast carcinomas: a single-institution series of 2033 consecutive cases documented in large-format histology slides.

A large-format histology technique represents the most convenient method for documenting and assessing the subgross morphological prognostic parameters of breast cancer (i.e., the distribution of the tumor's invasive and in situ components, disease extent, and tumor size), especially when used in conjunction with systematic radiological-pathological correlation. Here we report a consecutive series of 2033 breast carcinomas operated on in Dalarna, Sweden, with a particular focus on these subgross parameters. We separately analyzed the distributions of the in situ and invasive components of the tumors and then combined these into an aggregate pattern when both components were present. We found that 40% of breast carcinomas had a simple (unifocal) subgross morphology, while 60% had a complex morphology presenting with multifocal or diffuse components. Extensive tumors (occupying a total volume of breast tissue with the greatest dimension being ≥ 40 mm) were more common in complex cases, occurring in 66% of multifocal cases and 88% of diffuse cases, compared with only 5% of unifocal cases. Compared with luminal A-like tumors, HER2-expressing tumors exhibited a significantly larger extent. Triple-negative and basal-like carcinomas tended to have a larger tumor size (based on the largest dimension of the largest invasive focus). In this report, we discuss the prognostic impact of these parameters and the necessity of their correct assessment in the diagnostic routine.

Validation and reliability of the Malaysian English version of the psychosocial impact of dental aesthetics questionnaire for adolescents.

BACKGROUND: The Malay version of the Psychosocial Impact of Dental Aesthetics Questionnaire has been validated for use by Malaysian adolescents. Although Malay is their national language, English is widely used as the lingua franca among Malaysians of different ethnicities. This study aimed to validate an English version of the PIDAQ adapted for use by Malaysian adolescents to optimize data capture from adolescents who prefer English as the medium for communication. METHODS: The published English version of PIDAQ was pilot tested on 12- to 17-year-old adolescents, resulting in a few modifications to suit the Malaysian variety of English. Psychometric properties were tested on 393 adolescents who attended orthodontic practices and selected schools. Malocclusion was assessed using the Malocclusion Index, an aggregation of Perception of Occlusion Scale and the Aesthetic Component of the Index of Orthodontic Treatment Need, by the subjects (MI-S) and investigators (MI-D). Data were analysed for internal consistency and age-associated invariance, discriminant, construct and criterion validities, reproducibility and floor and ceiling effects using AMOS v.20 and SPSS v.20. RESULTS: The item Don't like own teeth on video of the Aesthetic Concern (AC) subscale was not relevant to a large proportion of participants (11.7%). Therefore, it was removed and the Malaysian English PIDAQ was analysed based on 22 items instead of 23 items. Confirmatory factor analysis showed good fit statistics (comparative fit index: 0.902, root-mean-square error of approximation: 0.066). Internal consistency was good for the Dental Self-Confidence, Social Impact and Psychological Impact subscales (Cronbach's alpha: 0.70-0.95) but lower (0.52-0.62) though acceptable for the AC subscale as it consisted of only 2 items. The reproducibility test was acceptable (intra-class correlations: 0.53-0.78). For all PIDAQ subscales, the MI-S and MI-D scores of those with severe malocclusion differed significantly from those with no or slight malocclusion. There were significant associations between the PIDAQ subscales with ranking of perceived dental appearance, need for braces and impact of malocclusion on daily activities. There were no floor or ceiling effects. CONCLUSION: The adapted Malaysian English PIDAQ demonstrated adequate psychometric properties that are valid and reliable for assessment of psychological impacts of dental aesthetics among Malaysian adolescents.

Molecular phenotype of the foci in multifocal invasive breast carcinomas: intertumoral heterogeneity is related to shorter survival and may influence the choice of therapy.

BACKGROUND: Multiple synchronous, ipsilateral, invasive foci of breast carcinomas are frequent and are associated with a poorer prognosis. Few studies have investigated the prognostic and therapeutic implications of heterogeneity of such foci. METHODS: The authors reviewed the tumor type, grade, and size of all invasive foci in a series of 110 multifocal breast carcinomas documented on large-format slides. Molecular phenotype was determined by immunohistochemistry in tissue microarray blocks using 3 classification systems. The survival of patients who had tumors with microscopic (tumor type and/or grade) heterogeneity and of those who had tumors with phenotypic heterogeneity was compared with the survival of patients who had multifocal homogeneous tumors using Kaplan-Meier curves. The hazard ratio of dying from breast cancer was also calculated. RESULTS: Intertumoral heterogeneity in tumor type and grade was detected in 16 of 110 tumors (14.6%) and in 6 of 110 tumors (5.5%), respectively. The molecular phenotype of invasive tumor foci within the same breast differed in 10% to 12.7% of patients (11-14 of 110 tumors), depending on the classification system used. Patients who had phenotypically heterogeneous, multifocal cancers had a greater risk of dying from disease (HR=2.879; 95%CI=1.084-7.649; P = .034) and had significantly shorter survival (P = .016). Phenotypic differences were most common in patients who had tumors that were homogeneous in terms of tumor type (11 of 18 tumors) and histology grade (14 of 18 tumors). Phenotyping additional tumor foci had the potential to influence the therapeutic decisions in up to 8 patients. CONCLUSIONS: Phenotyping more than 1 invasive focus of multifocal breast carcinomas only if the individual foci deviate microscopically appears to be insufficient, because phenotypic intertumoral heterogeneity may be observed in microscopically identical foci and has potential prognostic and therapeutic consequences.

Multifocal breast cancer documented in large-format histology sections: long-term follow-up results by molecular phenotypes.

BACKGROUND: The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail. METHODS: In total, 444 consecutive invasive breast cancers that were documented in large-format histology slides and worked up with detailed radiologic-pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes. RESULTS: Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14-fold respectively 2.75-fold risk of cancer-related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)-positive cancers; estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) cancers; or basal-like cancers had a 2.18-fold, 2.33-fold, and 4.07-fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2-positive, and basal-like cancers were associated with significantly better long-term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple-negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant. CONCLUSIONS: Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal-like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters.

Comparison of the subgross distribution of the lesions in invasive ductal and lobular carcinomas of the breast: a large-format histology study.

To compare the lesion distribution and the extent of the disease in ductal and lobular carcinomas of the breast, we studied 586 ductal and 133 lobular consecutive cancers. All cases were documented on large-format histology slides. The invasive component of ductal carcinomas was unifocal in 63.3% (371/586), multifocal in 35.5% (208/586), and diffuse in 1.2% (7/586) of the cases. The corresponding figures in the lobular group were 27.8% (37/133), 45.9% (61/586), and 26.3% (35/133), respectively. When the distribution of the in situ and invasive component in the same tumors was combined to give an aggregate pattern, the ductal carcinomas were unifocal in 41.6% (244/586), multifocal in 31.6% (185/586), and diffuse in 26.8% (157/586) of the cases. The corresponding figures in the lobular category were 15.0% (20/133), 54.2% (72/133), and 30.8% (41/133), respectively. Ductal cancers were extensive in 45.7% (268/586), lobular in 65.4% (87/133) of the cases. All these differences were statistically highly significant (P < 0.0001). While the histological tumor type itself (ductal versus lobular) did not influence the lymph node status, multifocal and diffuse distribution of the lesions were associated with significantly increased risk of lymph node metastases in both ductal and lobular cancers.

Breast cancer multifocality, disease extent, and survival.

The prognostic information implied in subgross morphologic parameters such as lesion distribution (unifocal, multifocal, or diffuse) and disease extent in breast cancer has remained largely unexplored in the literature. We aimed to test whether these parameters influence survival in breast carcinoma. The parameters were assessed in a series of 574 cases, all documented in large-format histology sections. We used Cox proportional hazards regression accompanied by Kaplan-Meyer survival curves, with P < .05 regarded as significant. The invasive component was unifocal in 62% (311/499), multifocal in 24% (122/499), and diffuse in 5% (26/499) of the cases. Combining the in situ and invasive tumor components resulted in 48% (274/574) unifocal, 25% (141/574) multifocal, and 20% (117/574) diffuse tumors. Sixty percent (347/574) of the tumors were categorized as having limited extent (occupying an area <40 mm in largest dimension) and 29% (164/574) as extensive. Highly significant (P < .0001) differences were observed in 10-year disease-specific cumulative survival among the cases with unifocal, multifocal, and diffuse invasive (89.6%, 76.0%, and 63.6%, respectively) and combined (92.3%, 82.3%, and 75.7%, respectively) lesion distribution. Patients with extensive tumors exhibited a significantly lower cumulative survival (P < .0001) compared with those with limited extent (91.6% and 75.5%) and a statistically significantly 1.89-fold (95% confidence interval, 1.07-3.37; P = .03) risk for breast cancer death after controlling for tumor attributes, type of surgery, and adjuvant therapy. The hazard ratio for breast cancer death for mutifocal and/or diffuse tumors versus unifocal ones was 1.96 (95%; 1.11-3.48; P = .02) after controlling for the same factors. Lesion distribution and disease extent represent important independent survival-related prognostic parameters in breast carcinoma.

Molecular phenotypes of unifocal, multifocal, and diffuse invasive breast carcinomas.

We analyzed the subgross distribution of the invasive component in 875 consecutive cases of breast carcinomas using large-format histology sections and compared the immunophenotype (estrogen and progesterone receptor expression, HER2 overexpression and expression of basal-like markers, CK5/6, CK14, and epidermal growth factor receptor) in unifocal, multifocal, and diffuse tumors. Histology grade and lymph node status were also analyzed. Unifocal invasive carcinomas comprised 58.6% (513/875), multifocal invasive carcinomas 36.5% (319/875), and diffuse invasive carcinomas 4.9% (43/875) of the cases. The proportion of lymph node-positive cases was significantly higher in multifocal and diffuse carcinomas compared to unifocal cancers, but no other statistically significant differences could be verified between these tumor categories. Histological multifocality and diffuse distribution of the invasive tumor component seem to be negative morphologic prognostic parameters in breast carcinomas, independent of the molecular phenotype.

The distribution of lesions in 1-14-mm invasive breast carcinomas and its relation to metastatic potential.

We analyzed 301 consecutive cases of 1-14-mm invasive breast carcinomas documented in large-format histological sections to determine the distribution of invasive and in situ foci. We also aimed to determine whether this distribution was related to the frequency of demonstrable vascular invasion and lymph node metastases. One third of the carcinomas (31.9%, 96 cases) had a multifocal invasive component and a more than doubled relative risk of vascular invasion (RR = 2.3642, 95% confidence interval (CI) = 1.5077-3.7073) and lymph node metastasis (RR = 2.7760, 95% CI = 1.6337-4.7171) compared to unifocal invasive carcinomas. Invasive carcinomas with diffuse in situ component had an elevated relative risk for vascular invasion (RR = 2.2201, 95% CI = 1.4049-3.5083) and lymph node metastasis (RR = 1.9201, 95% CI = 1.1278-3.2691) compared to those with unifocal or multifocal in situ lesions. However, multifocality of the invasive component was associated with a substantially elevated risk of vascular invasion and lymph node metastasis, even in cases with diffuse in situ component. Similar observations were made in the 1-9- and 10-14-mm invasive carcinoma subgroups. These findings indicate that lesion distribution has prognostic relevance for 1-14-mm invasive breast carcinomas and underline the importance of using special techniques in breast pathology for proper assessment of this parameter.

Radiological-pathological correlation in diagnosing breast carcinoma: the role of pathology in the multimodality era.

Breast carcinoma is a lobar disease, as the simultaneously or asynchronously appearing often multiple tumor foci originate from a single sick breast lobe. In its initial phase, the spatial pattern of malignant transformation may be lobar (targeting the entire lobe), segmental (targeting a segment) or terminal (targeting distant terminal ductal-lobular units) within the sick lobe. All these variations are properly characterized by the following parameters: the extent of the disease (the volume of the tissue containing all the actually present malignant structures within the breast), the distribution of the lesions within this tissue (unifocal, multifocal or diffuse, separately for in situ and invasive component), the size of the tumor (corresponding to the largest diameter of the largest invasive focus) and the exact localization of the lesion(s). In addition, intra- and intertumoral heterogeneity have to be noticed, if evident. Combining the results of different imaging modalities (mammography, ultrasound, magnetic resonance imaging) the radiologist may compensate the limitations of individual methods. This multimodality approach leads to more accurate radiological size measurement, more accurate assessment of the distribution of the lesions and disease extent. This represents a challenge for pathologists as the traditional histopathology method based on fragmentation and sampling of macroscopically suspicious lesion(s) is clearly insufficient for modern postoperative radiological-pathological correlation. There is a clear need for more complete examination of the excised tissue and for a three-dimensional reconstruction of the finding, preferably using continuous large tissue slices and two and three-dimensional large-format histological sections. Discordant results may still appear as a consequence of failure in radiological-pathological correlation or related to certain tumor subtypes as invasive lobular carcinoma of diffuse type, low grade in situ lesions or micropapillary ductal in situ carcinoma.

Role of interceptive orthodontics in early mixed dentition.

Early orthodontic interventions are often initiated in the developing dentition to promote favourable developmental changes and remove or suppress those that are unfavourable. Early interceptive orthodontics can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. It also improves self-esteem in the subjects and parental satisfaction. Early detection and appropriate referral of cases requiring interceptive orthodontics are important. However, lack of awareness among school children, parents and primary-care personnel (dental nurses and dental officers) may result in patients not being referred for timely interceptive intervention. This article presents a general view of the scope of interceptive orthodontics that can be carried out in early mixed dentition, i.e. when the permanent incisors and molars are erupting into the oral cavity.