Unifocal Cases Research Articles

E-Cadherin and Snail Immunohistochemical Expression in Multiple Ipsilateral Breast Carcinoma Disease

Abstract Background As compared to invasive breast cancer- no special type (IBC-NST), Invasive lobular cancer (ILC) traditionally shows loss of function of the E-cadherin- catenin membrane complex, frequent downregulation of E-cad expression and is significantly more associated with Multiple Ipsilateral Breast Carcinoma (MIBC). Nevertheless, E cadherin downregulation was also described in MIBC with IBC-NST phenotype. MIBC was suggested to have a more aggressive biologic nature than unifocal disease, Epithelial mesenchymal transition (EMT) has been suggested as an attribute to such poorer prognosis. The transcription factor Snail commonly acts as one of the earliest switches of the EMT process and E-cadherin downregulation is one of its major downstream effects. Causation and association links between EMT and MIBC in different types of breast cancer needs further elucidation. Objective to investigate whether the association betweenE-cadherin downregulation and MIBC is attributed to EMT and whether such association and expression of EMT markers is differentially presented in ILC and IBC-NST. Methods This study was conducted retrospectively on 77 breast cancer cases diagnosed at Ain Shams University Hospitals (2012-2022). We included all ILC cases meeting study criteria (20 unifocal, 14 MIBC) and randomly selected sets of IBC- NST cases (13 unifocal, 16 MIBC) and mixed ductolobular IBC (7 unifocal, 7 MIBC). Immunohistochemical expression of E-cadherin and Snail was evaluated and compared in different study groups with subsequent statistical analysis. Results E- cadherin expression showed 15/40 (37.5%) negative expression, 15/40 (37.5%) with low expression, and 10/40 (25%) with high expression in the unifocal group, compared to 14/37 (37.8%) negative result, 13/37 (35.1%) low E-cadherin expression, and 10/37 (27%) with high E-cadherin expression in the MIBC group. There was no significant difference in E-cadherin expression regarding focality neither in all cases (p-value: 0.97) nor in each of the histological subgroups (p-values: 0.34 for IBC- NST, 1.00 for mixed, 0.2 for ILC). On the other hand, Snail expression was extensive in 24/37 MIBC cases (64.86%) as compared to 17/40 unifocal cases (42.5%), this was statistically significant (p-value: 0.038). Conclusions E-cadherin downregulation doesn’t seem to contribute to MIBC whether ILC, mixed or IBC-NST, however snail overexpression is significantly associated with MIBC. This suggests that EMT may have a role in multiplicity of IBC.

Clinicopathological spectrum of central nervous system germ cell tumors: A single-institution retrospective study.

Central nervous system germ cell tumors (CNSGCTs) though rare is the second most common extragonadal site for GCTs. To determine the clinicopathological features of CNSGCTs diagnosed at our center. A retrospective study of all histologically diagnosed CNSGCTs, during 2006-2019. The patients' data were retrieved from the hospital information systems and analyzed. Data on categorical variables were analyzed as percentages, and data on continuous variables calculated as mean. Chi-square test or Fisher's exact test was used to study association between variables. Of the total 34 cases with CNSGCT, age ranged from 1 to 27 years, majority in the second decade (19/34; 56%). Male: female (M: F) ratio was 1.6:1. Single site involvement was seen in 27 cases (27/34; 79%), whereas seven (7/34; 21%) showed bi/multifocal involvement. Among the unifocal cases, common sites involved were suprasellar (12/27; 44.4%), closely followed by the pineal (10/27; 37%). All multifocal tumors affected suprasellar compartment, being bifocal with pineal in four cases. A male gender predilection was noted among pineal region (9/10;90%) and multifocal tumors (5/7;71%). Germinoma was the commonest subtype (21/34; 61.8%) with male gender predilection (17/21; 81%) (M: F =4.3:1), with female predilection seen among mixed GCTs (MGCTs) (8/10; 80%) (M: F =1:4) and suprasellar location (M: F =1:2). Serum tumor markers (25 cases) and CSF markers (7 cases) were concordant with histology in all, except two cases. Though histology and immunohistochemistry were diagnostic, correlation between serum and/or CSF marker was essential to rule out GCT component(s) that may be missed on biopsy due to sampling error.

A Girl with Limp and Rash on the Palms and Soles.

A Girl with Limp and Rash on the Palms and Soles.

Digital breast tomosynthesis: sensitivity for cancer in younger symptomatic women.

Full-field digital mammography (FFDM) has limited sensitivity for cancer in younger women with denser breasts. Digital breast tomosynthesis (DBT) can reduce the risk of cancer being obscured by overlying tissue. The primary study aim was to compare the sensitivity of FFDM, DBT and FFDM-plus-DBT in women under 60 years old with clinical suspicion of breast cancer. This multicentre study recruited 446 patients from UK breast clinics. Participants underwent both standard FFDM and DBT. A blinded retrospective multireader study involving 12 readers and 300 mammograms (152 malignant and 148 benign cases) was conducted. Sensitivity for cancer was 86.6% with FFDM [95% CI (85.2-88.0%)], 89.1% with DBT [95% CI (88.2-90%)], and 91.7% with FFDM+DBT [95% CI (90.7-92.6%)]. In the densest breasts, the maximum sensitivity increment with FFDM +DBT over FFDM alone was 10.3%, varying by density measurement method. Overall specificity was 81.4% with FFDM [95% CI (80.5-82.3%)], 84.6% with DBT [95% CI (83.9-85.3%)], and 79.6% with FFDM +DBT [95% CI (79.0-80.2%)]. No differences were detected in accuracy of tumour measurement in unifocal cases. Where available, DBT merits first-line use in the under 60 age group in symptomatic breast clinics, particularly in women known to have very dense breasts. This study is one of very few to address the accuracy of DBT in symptomatic rather than screening patients. It quantifies the diagnostic gains of DBT in direct comparison with standard digital mammography, supporting informed decisions on appropriate use of DBT in this population.

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 ≥ 40mm) 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.

Chronic Non-bacterial Osteomyelitis: A Review.

Chronic non-bacterial osteomyelitis (CNO) is a rare auto-inflammatory bone disorder, with a prevalence of around one in a million patients. In the more severe form, it is referred to as chronic recurrent multifocal osteomyelitis (CRMO). We present the current knowledge on epidemiology, pathophysiology as well as diagnostic options and treatment regimens. CNO/CRMO most commonly affects children and lesions are often seen in the metaphyseal plates of the long bones, but cases have been described affecting all age groups as well as lesions in almost every bone. It is, therefore, a disease that clinicians can encounter in many different settings. Diagnosis is mainly a matter of exclusion from differential diagnoses such as bacterial osteomyelitis and cancer. Magnetic resonance imaging is the best radiological method for diagnosis coupled with a low-grade inflammation and a history of recurring episodes. Treatment is based on case reports and consists of alleviating symptoms with non-steroidal anti-inflammatory drugs since the disease is often self-limiting. Recently, more active treatments using either bisphosphonates or biological treatment are becoming more common, to prevent long term bone damage. In general, due to its rarity, much remains unclear regarding CNO/CRMO. We review the known literature on CNO/CRMO and propose areas of interest as well as possible ways to make current diagnostic criteria more detailed. We also find unifocal cases of the jaw to be a possible sub-type that may need its own set of criteria.

Patient characteristics and risk factors for central serous chorioretinopathy: an analysis of 811 patients

AimsTo determine the demographic and morphological characteristics of patients with central serous chorioretinopathy (CSC) and describe risk factors for CSC.MethodsWe retrospectively reviewed medical records of 811 patients with CSC and...

Comparison of [18 F]FDG PET/CT and MRI in the diagnosis of active osteomyelitis

In diagnosing osteomyelitis (OM) both MRI and [18F]FDG PET-CT proved to be accurate modalities. In anticipation of the advent of hybrid PET/MRI scanners we analyzed our patient group to give direction to future imaging strategies in patients with suspected OM. In this retrospective study all patients of a tertiary referral center who underwent both an MRI and a PET for the diagnosis of OM were included. The results of those scans were evaluated using patient's histology, microbiological findings, and clinical/radiological follow-up. Additionally, ROC curve analysis of the SUVmax and the SUVmax ratio on the PET scans was performed. Two imaging strategies were simulated: first MRI followed by PET, or vice versa. Twenty-seven localizations in 26 patients were included. Both MRI and PET were shown to be accurate in our patients for the qualitative detection of OM. A cut-off value for the SUVmax of 3 gave optimal results (a specificity of 90% with a sensitivity of 88%). The SUVmax ratio gave a worse performance. The two simulated imaging strategies showed no difference in the final diagnosis in 20 out of 27 cases. Remarkably, 6 equivocal cases were all correctly diagnosed by the second modality, i.e., PET or MRI. Both MRI and [18F]FDG PET were accurate in diagnosing OM in a tertiary referral hospital population. Simulation of imaging strategies showed that a combined sequential strategy was optimal. It seems preferable to use MRI as a primary imaging tool for uncomplicated unifocal cases, whereas in cases with (possible) multifocal disease or a contraindication for MRI, PET is preferred. This combined sequential strategy looks promising, but needs to be confirmed in a larger prospective study.

OP0006 A Large National Cohort of French Patients with Chronic Recurrent Multifocal Osteitis

BackgroundFrequency of chronic recurrent multifocal osteomyelitis (CRMO), also known as nonbacterial osteomyelitis, seems to be underestimated and often leads to consequential residual impairments.ObjectivesThe aim of this study was to collect...

Axillary Lymph Node Status in Unifocal, Multifocal, and Diffuse Breast Carcinomas: Differences Are Related to Macrometastatic Disease

Multifocality in breast carcinoma is associated with an increased propensity to metastasis. However, it is not clear whether this propensity manifests in the form of macrometastases or as presumably less-significant low-volume metastatic disease. A total of 948 cases of invasive breast carcinoma documented in large-format histology sections and assessed with detailed radiologic-pathologic correlation were categorized as unifocal, multifocal, or diffuse on the basis of the subgross distribution of the invasive component. Rates of macrometastases (>2 mm), micrometastases (0.2-2 mm), and isolated tumor cells (<0.2 mm) in these categories were compared. The influence of tumor size and histology grade on lymph node positivity rates was also tested. Macrometastases were present in 20.4% (112 of 550) of unifocal, 48.3% (172 of 356) of multifocal, and 61.9% (26 of 42) of diffuse cases (P < 0.0001). Among the macrometastatic cases, more than three nodes were involved in 18.9% (21 of 112) of unifocal, 35.5% (61 of 172) of multifocal, and 50.0% (13 of 26) of diffuse cases. The rates of micrometastases (5.1, 5.1, and 2.4% unifocal, multifocal, and diffuse, respectively) and isolated tumor cells (4.5, 3.7, and 2.4% unifocal, multifocal, and diffuse, respectively) were low and similar in all examined categories. The relative risk (RR) of having macrometastatic disease was approximately doubled (RR 2.3726, P < 0.0001) in multifocal and tripled (RR 3.0562, P < 0.0001) in diffuse compared to unifocal cases. The findings were similar for all size categories, tumor grade categories, and sentinel lymph nodes, as well as all examined lymph nodes. The significantly increased lymph node positivity rates in multifocal and diffuse invasive breast carcinomas results from large-volume macrometastatic disease.

Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma.

For unifocal invasive breast carcinoma, increasing tumor diameter predictably correlates with a greater frequency of lymph node involvement, thereby facilitating treatment decisions. In invasive breast tumors presenting with multiple nodules, however, it is unclear whether tumor size correlates with lymph node dissemination in a similar manner. The authors analyzed a series of 101 invasive breast carcinomas presenting with multiple macroscopically apparent lesions (2 foci: n = 77; 3: n = 20; 4: n = 4). Two different assessments of the tumor size (diameter of largest focus and combined diameter of all the foci) were then correlated with the status of axillary lymph nodes. For comparison with unifocal tumors, the authors used both external and internal control series (the latter consisting of 469 patients from their institution). The associations between lymph node status, tumor size, and multifocality were modeled using univariate and multivariate logistic regression, for each modality of tumor size assessment. The logistic curves for multifocal and unifocal tumors were significantly different when the largest diameter was used as a tumor size estimate. Multifocal cases had higher frequencies of lymph node involvement than unifocal lesions of similar size category. In a multivariate logistic regression, the odds ratio of positive lymph node status in multifocal versus unifocal cases was 2.8 using largest diameter as a tumor size estimate (P < 0.0001). When the combined diameter assessment was used, however, the regression curve of multifocal cases was similar to that of unifocal cases, and the frequency of lymph node positivity was not significantly different in multifocal versus unifocal cases of the same size (odds ratio, 1.4; P = 0.13). The authors' results show that, if aggregate diameters are used, unifocal and multifocal breast carcinomas are similar with respect to frequency of regional lymph node metastasis. Currently used algorithms, which use the diameter of the largest nodule, result in understaging of multifocal breast carcinomas due to underestimation of actual tumor size.

Presumed Pneumocystis carinii Choroiditis: Unifocal Presentation, Regression with Intravenous Pentamidine, and Choroiditis Recurrence

AbstractPneumocystis carinii choroiditis is a well-documented but rare infection that has been described as a bilateral, multifocal process. Treatment efficacy has not been well established. In this report, three cases of presumed P. carinii choroiditis that developed during aerosolized pentamidine therapy for the prophylaxis of P. carinii pneumonia are described. All patients had unilateral choroiditis, and two patients were first observed to have unifocal choroiditis. In all patients, choroidal lesions decreased in size with intravenous pentamidine treatment. Choroiditis exacerbated in the two unifocal cases after the frequency of maintenance intravenous pentamidine therapy was decreased. P. carinii choroiditis may appear as a unifocal, unilateral lesion that may represent an earlier stage of infection than previously described. Intravenous pentamidine therapy appears to control P. carinii choroiditis but may need to be continued to prevent exacerbation. Patients receiving prophylactic aerosolized pentamidine therapy are not protected against extrapulmonary disease, and presumed P. carinii choroiditis may serve as a marker for disseminated infection.