Invasive Ductal Carcinoma Research Articles

Mammary Paget's Disease Mimicking Benign and Malignant Dermatological Conditions: Clinical Challenges and Diagnostic Considerations.

Mammary Paget's disease (MPD) or Paget's disease of the breast is a rare dermatological malignancy of the nipple-areolar complex that manifests with a spectrum of symptoms spanning from itching and redness to more severe indications such as breast lump, nipple-areolar complex destruction, or nipple discharge. It is predominantly associated with an underlying ductal carcinoma in situ or invasive ductal carcinoma. MPDoften masquerades as other benign and malignant dermatological conditions, including eczema, atopic dermatitis, psoriasis, and squamous and basal cell carcinomas, leading to delayed diagnosis and inappropriate treatment. Only one-third of the patients present with a palpable lump; therefore, advanced age with chronic and unilateral lesions should raise concern for MPD. Our review article presents case reports of MPD imitating other skin conditions and underscores the key findings of clinical features and diagnostic workup to help differentiate the condition. A literature review revealed that studies emphasize caution regarding the sole use of mammography and ultrasound in diagnosing MPD, particularly in cases lacking a palpable lump. This highlights the MRI as a superior and more accurate imaging tool. However, any suspicious lesion must be biopsied to allow histopathological and immunohistochemical examination, since there are some cases where MRI findings were negative in the presence of a biopsy-proven MPD. This highlights the need for clinicians to investigate any suspicious lesion of the nipple or breast using the complete triple assessment approach to exclude an underlying malignancy. It is imperative to establish therapeutic guidelines to approach any nipple lesion to minimize the risk of misdiagnosing any underlying cancer, which can be potentially fatal if left alone.

Oncoplastic Breast-Conserving Surgery in African Women: A Systematic Review.

Breast cancer is the most frequently diagnosed cancer in women worldwide. Surgery is a major treatment modality for breast cancer, and over the years, breast-conserving surgeries with breast radiation have shown similar outcomes with mastectomy. Not much is known about the frequency and outcome of breast-conserving surgery in Africa. This systematic review provides a comprehensive summary of the evidence evaluating cosmetic and oncologic outcomes after oncoplastic breast-conserving surgery (OBCS) for breast cancer in African women. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases were systematically searched for studies on African women undergoing OBCS. The oncologic and cosmetic outcomes, as well as the localization and reconstruction techniques, were evaluated. Descriptive statistics were used to summarize the frequency and proportions of the extracted variables. The literature search yielded 266 articles but only 26 of these were included in the review. Majority of the studies were from Egypt and South Africa. These studies collectively evaluated 1,896 patients with a mean age of 48.2 years and a mean follow-up period of 36.9 months. The most common histopathology was T2 (71.4%) invasive ductal carcinoma. Hook wire localization was the most common technique used for nonpalpable lesions in 85.3% of patients. Of the studies reporting oncoplastic technique, the latissimus dorsi volume replacement technique was the most reported (15%). Most patients were satisfied with their cosmetic outcome. Seroma was the most common postoperative complication (44.6%). Among studies that reported oncologic outcome data, the crude overall survival and disease-free survival were 93.1% and 89.4%, respectively. This systematic review revealed that the outcome of OBCS in African women compares with that in developed countries.

Immunohistochemical Expression of Caspase1 and Epidermal Growth Factor Receptor in Invasive Breast Carcinoma and Their Biological and Prognostic Associations.

Despite advances in breast carcinoma therapies, drug resistance mechanisms as anti-apoptosis and anti-pyroptosis limit the application of these therapies. This work assesses the immunohistochemical (IHC) expression of Caspase1 and EGFR in breast carcinoma and analyzes their clinicopathological associations as prognostic markers and potential therapeutic targets. Caspase1/EGFR expression patterns are utilized to specify breast carcinoma patients who may benefit from these therapies. After reviewing the hematoxylin and eosin-stained slides and the routine breast carcinoma IHC stains (estrogen receptors, progesterone receptors, HER2/NEU, Ki-67) by two pathologists and preparation of tissue microarray blocks, anti-Caspase-1 and EGFR IHC staining was performed using Horseradish Peroxidase (HRP) technique. Intensity and percentage-based scoring was applied dividing the 153 included breast carcinomas into Caspase1-negative and positive expression groups; and EGFR low and overexpression groups. Groups were statistically analyzed in relation to age, tumor size, histological and molecular subtype, grade, nodal status, metastasis/recurrence, TNM stage and Ki-67 proliferation index. Kaplan-Meier's analysis was used to compare disease-free survival (DFS) and overall survival (OS). Combined patterns based on Caspase1 and EGFR expression status were created to stratify patients into prognostic groups. Caspase1 was positive in 54.2% of breast carcinomas and its positivity was significantly associated with smaller tumor size, absence of metastasis/recurrence, luminal A and B molecular subtypes and longer OS (p<0.05). EGFR overexpression was detected in 32.7% of carcinomas and was significantly associated with larger tumor size, TNBLBC and a shorter OS (p<0.05). Caspase1-negative/EGFR-overexpression pattern comprised 14.4% of carcinomas and had the worst prognostic associations including larger tumor size, metastasis/recurrence, TNBLBC subtype and shortest OS (p=0.002, 0.002, 0.004 and ≤0.001 respectively). Conclusions: Combined Caspase1/EGFR IHC expression may provide a tool for selection of patients who benefit from combined EGFR-inhibitors with miR-155-5p down-regulators or photodynamic therapy via induction of apoptosis/pyroptosis in EGFR-overexpression carcinomas through enhanced Caspase1 signaling.

Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma insitu. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Invasive intraductal oncocytic papillary neoplasms (IOPN) and adenocarcimoma arising from intraductal papillary mucinous neoplasms (A-IPMN) of the pancreas: comparative analysis of clinicopathological features, patterns of recurrence and survival: a multicentre study

BackgroundIntraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. MethodsConsecutive patients undergoing pancreatic resection (2010–2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). Results415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). ConclusionsInvasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.

Mean Apparent Propagator MRI: Quantitative Assessment of Tumor-Stroma Ratio in Invasive Ductal Breast Carcinoma.

Purpose To determine whether metrics from mean apparent propagator (MAP) MRI perform better than apparent diffusion coefficient (ADC) value in assessing the tumor-stroma ratio (TSR) status in breast carcinoma. Materials and Methods From August 2021 to October 2022, 271 participants were prospectively enrolled (ClinicalTrials.gov identifier: NCT05159323) and underwent breast diffusion spectral imaging and diffusion-weighted imaging. MAP MRI metrics and ADC were derived from the diffusion MRI data. All participants were divided into high-TSR (stromal component < 50%) and low-TSR (stromal component ≥ 50%) groups based on pathologic examination. Clinicopathologic characteristics were collected, and MRI findings were assessed. Logistic regression was used to determine the independent variables for distinguishing TSR status. The area under the receiver operating characteristic curve (AUC) and sensitivity, specificity, and accuracy were compared between the MAP MRI metrics, either alone or combined with clinicopathologic characteristics, and ADC, using the DeLong and McNemar test. Results A total of 181 female participants (mean age, 49 years ± 10 [SD]) were included. All diffusion MRI metrics differed between the high-TSR and low-TSR groups (P < .001 to P = .01). Radial non-Gaussianity from MAP MRI and lymphovascular invasion were significant independent variables for discriminating the two groups, with a higher AUC (0.81 [95% CI: 0.74, 0.87] vs 0.61 [95% CI: 0.53, 0.68], P < .001) and accuracy (138 of 181 [76%] vs 106 of 181 [59%], P < .001) than that of the ADC. Conclusion MAP MRI may serve as a better approach than conventional diffusion-weighted imaging in evaluating the TSR of breast carcinoma. Keywords: MR Diffusion-weighted Imaging, MR Imaging, Breast, Oncology ClinicalTrials.gov Identifier: NCT05159323 Supplemental material is available for this article. © RSNA, 2024.

Clinical and Pathological Predictors of Recurrent Breast Cancer

Objectives: Recurrence of breast cancer is common. There are reported risk factors for recurrence which are patient age, tumor size, tumor grade, (lymph vascular invasion (LVI), extensive intraductal component (EIC), and margin status. Nodal involvement also contributes to the recurrence rate as well as hormonal status, and if the patient receives neoadjuvant/adjuvant therapy or not. The aim of this study is to look for the clinical and pathological predictors of patients who have recurrent breast cancer after surgical treatment. Methods: We conducted a retrospective cohort study at one center (Royal hospital) between 2010 to 2020 for patients who were treated surgically for nonmetastatic breast cancer. We collected the clinical which was mainly the age at the diagnosis and pathological predictors (final histopathology report of the surgical specimen) from the medical records system of the hospital after obtaining the ethical approval. Total sample size was 270 Omani patients. The primary endpoint was the time to locoregional recurrence or systemic recurrence as the first event. A multivariate analysis of the predictors was carried and a P-value of &lt; 0.05 was considered statistically significant with 95% CI. Results: Out of 270 patients with breast cancer who were surgically treated, 113 had recurrence and 157 had no recurrence. There were 104 patients with recurrence have invasive ductal carcinoma (IDC) and 9 patients with high-grade ductal carcinoma in situ (DCIS). The Mean age of patients with recurrence was 44.0 while in patients without recurrence was 48.3. The difference in age between the two groups is not statistically significant in predicting the recurrence (p = 0.816). ER, LVI, EIC, nodal involvement, grade, margin, and type of tumor were the significant predictors of recurrence by bivariate analysis. However, High grade (Hazard ratio (HR) = 3.823, 95% CI: 1.104-13.240; p = 0.034), EIC (HR = 17.407, 95% CI: 1.538-196.999; p = 0.021), and nodal involvement (HR = 2.314, 95% CI: 1.123-4.767; p = 0.023) remain the significant predictors for recurrent breast cancer in the multivariate Cox regression analysis. By using Kaplan-Meier, the median survival time was 132 months and the recurrence-free survival at two years was 88.0% (The recurrence rate = 12.0%). Conclusions: High grade, extensive intraductal component, and nodal involvement are significant predictors for breast cancer recurrence. The recurrencefree survival at 2 years is 88.0%. Our recommendation is a close follow-up for patients with these predictors.

Radiologist Accuracy in Predicting Pathology in Breast Imaging

Introduction: Breast cancer, the most prevalent cancer in women and second only to lung cancer in female mortality, has seen rising incidence, especially during the 1980s and 1990s due to increased mammography screening. Screening’s primary goal is early tumor detection, reducing mortality by over 40%. Yet, it has downsides, including false-positive cases of benign biopsies and potential increased patient anxiety and stress. The average recall rate from screening mammograms is 5-10%. Among women requiring biopsy, the anticipated rate of malignant findings range between 30-50%. With the evolution of image-guided breast biopsy techniques, concerns have risen regarding the escalating frequency of breast biopsies. The possible causes are overlapping imaging characteristics of benign and malignant pathologies, patients’ anxiety, litigation risk and radiologist years of experience. A radiologists’ ability to predict breast histology from imaging findings remains an understudied domain. This study’s core purpose is to comprehensively analyze the ability of a radiologist to predict benign versus malignant results to provide guidance in reducing the number of benign biopsies. Methods: This prospective study involved radiologists completing survey sheets when recommending biopsies and when performing the biopsy, predicting benign vs malignant, specific pathology, with confidence interval. Predictions were compared to the final biopsy results to determine accuracy. All patients who underwent biopsy at our institutions were included in the data. Data was categorized as either concordant or discordant when comparing predicted pathology results to actual. Results: The accuracy of radiologist prediction from initial diagnostic imaging when compared to actual pathology results in the study population is 71% (95% CI,61.8%-79.37%) with a sensitivity of 75 % (95% CI, 60.4%-86.36%). The accuracy of radiologist prediction at biopsy when compared to actual pathology results is 80.79% (95% CI, 75.89%-85.08%) with sensitivity of 79.77% (95% CI, 73%-85.49%). The accuracy of less to moderately experienced radiologists to highly experienced radiologists is similar, 78.2% vs 81.0%. Further analysis of specific pathology prediction reveals that fibroadenoma is the most common benign pathology encountered, the prediction of which by imaging alone/at biopsy is 65%/68%. In the malignant category, invasive ductal carcinoma is the most common pathology encountered where the prediction is 68%/85%. Conclusions: This data will potentially help radiologists gain confidence in watching likely benign lesions based on imaging features (assigned as BIRADS 3) to reduce benign biopsies.

CURRENT DRUG THERAPY OPTIONS FOR DISSEMINATED HER2-POSITIVE BREAST CANCER AT THE KAZAKH SCIENTIFIC RESEARCH INSTITUTE OF ONCOLOGY AND RADIOLOGY: A CLINICAL CASE

Relevance: Distant outcomes of treatment for Her2neu-positive metastatic breast cancer are improving due to access to innovative drug therapies. The study aimed to demonstrate the initial experience of treating a patient with progressive disseminated hormone receptor-positive breast cancer expressing HER2 (3+) and nearly exhausted options for anti-tumor drug therapy using trastuzumab deruxtecan. Methods: The paper describes a clinical case of a female patient born in 1977 who was diagnosed with Stage IV breast cancer (T1N1M1), invasive ductal carcinoma, and treated at the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan). Immunohistochemical luminal subtype “B” with Her2neu (3+) expression. Metastatic involvement of skeletal bones with pain syndrome, lungs, liver, axillary, parasternal, and para-mediastinal lymph nodes. Since June 2023, monoclonal antibody conjugate trastuzumab deruxtecan therapy was initiated. The efficacy of fifth-line therapy was assessed using RECIST 1.1 before and during treatment. According to RECIST 1.1., target lesions included a conglomerate of hyperplastic axillary lymph nodes on the right, measuring 1.6 cm, parasternal lymph node 1.6 cm, a lesion in the parenchyma of the lower lobe of the left lung 1.3 cm, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe 1.8 cm and 3.6 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes SLD 9.9 cm. Results: Pain syndrome was completely relieved after treatment. According to RECIST 1.1. in April 2024, after 11 courses of therapy, target lesions showed size reduction: conglomerate of hyperplastic axillary lymph nodes on the right decreased to 1.0 cm, lesion in the parenchyma of the lower lobe of the left lung increased to 2.7 cm, parasternal lymph node was not visualized, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe measured 1.6 cm and 2.7 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes were not visualized. Conclusion: According to the clinical study data (DESTINY-Breast02), applying antibody-drug conjugate (ADC) demonstrates better objective response and progression-free survival time in patients previously treated with trastuzumab and taxanes.

The Accuracy of Core Needle Biopsy in Determining Histological Type and Scarff- Bloom-Richardson Grade in Invasive Breast Cancer.

This 18-month retrospective study examined the accuracy of core needle biopsy (CNB) in diagnosing histological type and Scarff-Bloom-Richardson (SBR) grade in 110 invasive breast cancer patients at Rajshree Medical Research Institute, Bareilly. The study demonstrated 89.1% histological concordance between CNB and surgical specimens, with invasive ductal carcinoma identified with excellent accuracy. However, SBR grade concordance was moderate at 77.3%, suggesting CNB may not consistently reflect tumour aggressiveness. Statistics showed great sensitivity and specificity for histological typing, but CNB results should be interpreted cautiously, especially for grading and rare subtypes. CNB is still a useful diagnostic tool, although surgical examination may be needed to confirm and arrange treatment. Keywords: Core Needle Biopsy, Invasive Breast Cancer, Histological Type, SBR Grade

Rectal metastasis arising from breast cancer: a case report.

Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.

Evaluating Surgical Outcomes Between Estrogen Receptor Positive Invasive Lobular and Invasive Ductal Carcinoma of the Breast—A Propensity Matched Analysis

IntroductionInvasive lobular carcinoma (ILC) contributes significantly to the global cancer burden and is the most common of the histological “special types” of breast cancer. ILC has unique features setting it apart from the more common invasive ductal carcinoma (IDC). Despite differences, treatment algorithms do not consider histological differences. AimTo determine the differences in treatment and outcomes of ILC relative to IDC in a strict case-matched cohort study at a tertiary referral, specialist, breast cancer center. MethodsAll Estrogen receptor positive (ER+) ILCs from 1999 to 2015 were matched for; age, tumor size, grade, PR/HER2 status, nodal stage and metastases with ER+ IDCs from the same period. Surgical and systemic treatments were assessed along with overall (OS) and disease-free survival (DFS). Results762 cases in total were analyzed (1:1 matching; ILC:IDC). ILC cases were more often treated with mastectomy (37.5% vs. 28.6%, P .009) and those who received breast conserving surgery (BCS) more often had an incomplete resection (30.2% vs. 19.6%, P .01). IDC were more often treated with NACT (5.5% vs. 14.4%, P < .001). Mean DFS were similar between ILC and IDC; 148.3 vs. 141.4 months (P .112) but OS was significantly longer in the ILC group; 165.7 vs. 134 months (P .002). This trend was consistent among the subset of patients undergoing BCS. For ILC undergoing BCS, mean DFS was 129.8 vs. 128.3 months for IDC (P .418) and OS was 155.4 and 110.7 months respectively (P < .001). Incomplete resection at the time of index surgery did not alter the disease free or overall survival in either the ILC or IDC patients to a level that reached statistical significance. ConclusionIn this cohort study, the strict matching of ILC and IDCs for a number of prognostic indicators, demonstrates the impact of lobular histology with a clarity not previously observed. ILCs have comparable survival outcomes to patients with IDC but at the expense of more extensive index and revisional surgery. There is a need for awareness of these facts among surgeons and patients for optimal treatment prioritization and provision.

HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

A Study on Stromal Expression of CD10 Marker in Breast Carcinoma and Its Role as a Prognostic Marker in a Tertiary Care Center in South Kerala

Abstract Background and Aims: Breast cancer is one of the leading causes of mortality among women. The aim of our study is to evaluate the stromal expression of CD10 in invasive breast carcinoma and to find its relationship with other prognostic markers such as age, histopathologic grade, estrogen receptor (ER), progesterone receptor (PR), and HER2Neu status. Materials and Methods: A total of 51 cases of breast cancer were included in the study. Representative sections were taken and hematoxylin and eosin staining was done. Immunohistochemistry was performed with ER, PR, Her2neu, and CD10. Stromal expression of CD10 is positive when &gt;10% of stromal cells show cytoplasmic and membranous positivity in invasive breast carcinoma. This will be noted and statistically analyzed with different known prognostic markers of breast carcinoma. Results: Stromal CD10 positivity was seen in 74.5% of cases (45% were strongly positive and 29.5% were weakly positive). 25.5% of cases were negative. Positivity for ER, PR, and HER2, was 58.8%, 35.3%, and 27.5%, respectively. Stromal expression of CD10 was found to be significantly associated with ER negativity (P = 0.001) and PR negativity (P = 0.001). Increasing intensity was noted with few parameters such as postmenopausal status and histologic grade but could not show statistical significance. No correlation was found between CD10 overexpression with respect to the age, tumor size, lymph node positivity status, tumor stage and HER2Neu status. Conclusions: CD10 expression correlated strongly with well-established negative prognostic markers, ER/PR negativity, and higher tumor grade, thus indicating that CD10 can be used as an independent marker indicating poor prognosis. This study highlights the role of stromal CD10 expression in predicting prognosis and the relationship with other prognostic markers. Keeping the role stroma plays in predicting prognosis and tumor response, CD10 can be included as a routine prechemotherapy marker in breast carcinoma. Further studies should be performed to see the role stroma plays in hormonal expression and the usefulness of CD10 to predict treatment failure in breast carcinomas receiving neoadjuvant therapy.

Role of Pap Smear Cervical Cytology in the Diagnosis of Extrauterine Malignancies: Largest Study of 104 Cases from Tertiary Care Cancer Centre in India

Introduction: Extrauterine malignancies in cervical samples are rarely seen. It is important to differentiate these cells from those of primary uterine malignancies to determine appropriate line of further investigations and management. Literature on these lesions is limited largely restricted to case reports. The aim of the present study was to study the spectrum and cytomorphological features of extrauterine malignancies in cervical Pap smears. Materials and Methods: It is a retrospective and descriptive study conducted in Department of Cytopathology from January 2019 to July 2023. All cases of extrauterine malignancies with available cytology material were included in this study. All cases of primary uterine malignancies, i.e., uterine corpus or cervix confirmed by clinical, radiological, and histopathological examination were excluded. Results: 104 out of 11,674 cytology Pap smears were those of extrauterine malignancy. Diagnosis of extrauterine malignancy was given in 47.1% cases, 30.9% were reported as positive for malignancy without giving the possibility of an extrauterine origin, and 22.0% were reported as atypical glandular cells only. In 56 cases where Pap smear was the first investigation which led to the diagnosis. Most common extrauterine malignancy was adenocarcinoma principally from ovarian, colorectal, and vaginal origin. Other epithelial malignancies noted were urothelial carcinoma and invasive breast carcinoma. Among non-epithelial malignancies, we reported vaginal mucosal melanoma, cutaneous melanoma, acute leukaemia, and anaplastic large cell lymphoma. Conclusion: High index of suspicion, presence of squamous and glandular elements with no atypical features, and occasional clusters of cells with marked atypia and usually no necrosis in the background are helpful cytomorphological clues to raise suspicion for extrauterine malignancy. Correlation with serology, radiology, and immunocytochemistry can help in reaching final diagnosis.

Cadaveric Study: Sign of Leser-Trélat Associated with Breast Cancer

INTRODUCTION: Seborrheic keratoses (SK) is considered the most common benign skin lesions found in individuals that are middle aged and older. In dermatology practice, these lesions pose no threat to the individual but can be concerning for cosmetic and underlying malignancy reasons when they cover most of the skin surface. Of specific concern is the sign of Leser-Trélat, which has been documented as a cutaneous harbinger of underlying malignancy associated with proliferation of the size and/or number seborrheic keratoses. The rare sign is usually caused by malignancies such as gastrointestinal adenocarcinoma, but also lung, kidney, liver, or pancreatic cancer. This case report will describe the histology of the skin lesions in Lesar Trélat and analyze the current literature regarding its association with breast cancer, which is quite rare. RESOURCES: For this case study, a cadaver from the body donor program in Philadelphia College of Osteopathic Medicine (PCOM), South Georgia was used. Skin samples were sent to Colquitt Regional Center for processing, where sections were embedded in paraffin and were stained with H&amp;E stain. A pathologist reported histopathological findings of the skin lesions and the breast tissue samples. DESCRIPTION: Multiple SK lesions covering the face, abdomen, back, as well as both upper and lower extremities were observed in one of the cadavers in the gross anatomy laboratory. Due to the significant number of pigmented, verrucous lesions, the sign of Leser-Trélat was clinically postulated, later confirmed during routine laboratory dissection of the breast tissue. Histology sections confirmed not only multiple SK lesions in the skin, but also revealed an associated breast cancer in the form of an infiltrative ductal carcinoma. SIGNIFICANCE: The sign of Leser-Trélat is rare by itself and its association with breast cancer is even more uncommon. Once a clinician recognizes the multiple SK eruptions, the patient should be meticulously investigated for not only for an underlying GI malignancy, but also for other cancers like breast cancer. Additionally, a case report confirmed malignant melanoma that mimicked sign of Leser-Trélat, warranting the importance of further analyzing the pathology diagnosis when there is a proliferation of multiple seborrheic keratoses.Therefore, biopsy and histology diagnosis is crucial for ruling out both cutaneous as well as underlying malignancies and should be encouraged when patients present in clinic rather than assuming the typical benign characteristics of seborrheic keratosis.

Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.

Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested. IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed. Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma. Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma

Droplet digital PCR analysis of CDH13 methylation status in Slovak women with invasive ductal breast cancer

Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR− versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.

Multimodal Data-Driven Intelligent Systems for Breast Cancer Prediction

Cancer, a malignant disease, results from abnormalities in the body cells that lead to uncontrolled growth and division, surpassing healthy growth and stability. In the case of breast cancer, this uncontrolled growth and division occurs in breast cells. Early identification of breast cancer is key to lowering mortality rates. Several new developments in artificial intelligence predictive models show promise for assisting decision-making. The primary goal of the proposed study is to build an efficient Breast Cancer Intelligent System using a multimodal dataset. The aim is to to establish Computer-Aided Diagnosis for breast cancer by integrating various data.This study uses the TCGA "The Cancer Genome Atlas Breast Invasive Carcinoma Collection" (TCGA-BRCA) dataset, which is part of an ongoing effort to create a community integrating cancer phenotypic and genotypic data. The TCGA- BRCA dataset includes: Clinical Data, RNASeq Gene Data, Mutation Data, and Methylation Data. Both clinical and genomic data are used in this study for breast cancer diagnosis. Integrating multiple data modalities enhances the robustness and precision of diagnostic and prognostic models in comparison with conventional techniques. The approach offers several advantages over unimodal models due to its ability to integrate diverse data sources. Additionally, these models can be employed to forecast the likelihood of a patient developing breast cancer in the near future, providing a valuable tool for early intervention and treatment planning.