Low-Grade Adenosquamous Carcinoma of the Breast Masquerading as a Fibroepithelial Lesion on Core Biopsy: A Challenging Case.

INTRODUCTION: Diagnosing low-grade adenosquamous carcinoma (LGASC) presents significant challenges due to its subtle morphology, variable immunohistochemical expression, and resemblance to benign lesions like radial scar and complex sclerosing lesions. CASE PRESENTATION: We present a case of a 53-year-old woman with a subareolar mass initially thought to be a fibroepithelial neoplasm on core biopsies. Subsequent wide excision revealed LGASC with oestrogen receptor expression (weak to moderate intensity, 40% of tumour cells). CONCLUSION: These findings, rarely reported, highlight the difficulty of diagnosing LGASC on small tissue samples.

Human epidermal growth factor receptor 2 (HER2) status in breast cancer: practice points and challenges.

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancer benefits significantly from anti-HER2 targeted therapies. This highlights the critical need for precise HER2 immunohistochemistry (IHC) interpretation serving as a triage tool for selecting patients for anti-HER2 regimens. Recently, the emerging eligibility of patients with HER2-low breast cancers for a novel HER2-targeted antibody-drug conjugate (T-DXd) adds challenges to HER2 IHC scoring interpretation, notably in the 0-1+ range, which shows high interobserver and interlaboratory staining platform variability. In this review, we navigate evolving challenges and suggest practical recommendations for HER2 IHC interpretation.

Case report: Metastatic ovarian mucinous carcinoma to the breast: diagnostic challenges and pitfalls.

Metastases to the breast from extramammary sources are extremely rare, with the ovary, primarily high-grade serous carcinoma, being the most common origin. We report a case of breast metastases from advanced stage ovarian mucinous carcinoma in a 48-year-old female- a case hitherto unreported in the literature. The case is noteworthy for its atypical presentation marked by an areolar rash, clinically suggestive of Paget disease of the nipple. This unique clinical scenario, coupled with histopathological examination revealing in-situ-like carcinoma component, posed a diagnostic challenge in discerning the tumour origin. We emphasize the need for heightened awareness among pathologists to avoid misdiagnosing metastatic carcinomas as primary breast tumours, a potential pitfall with significant clinical implications.

HER2-low breast cancers: challenges in the interpretation of immunohistochemistry.

ABSTRACT: Overexpression of human epidermal growth factor receptor 2 (HER2) protein in breast cancers carries significant prognostic and therapeutic implications. Anti-HER2 blockade has shown to be a useful adjunct to surgery in treating HER2-positive tumours. Up till today, the HER2 immunohistochemistry (IHC) and in situ hybridisation (ISH) scoring algorithms are geared towards identifying HER2-positive cases. A recently published Phase III clinical trial (DESTINY-Breast04) has demonstrated that an antibody-drug conjugate (trastuzumab-deruxtecan) significantly reduced disease progression and death in patients with metastatic disease with IHC score 1+ or 2+ and without ISH amplification, defining a new category of cases known as HER2 low. At present, IHC scores 0, 1+ and 2+ show significant interobserver variability, and identifying HER2-low breast cancers may pose significant challenges with the current algorithms. More work is needed in this area to better define HER2-low breast cancers, target the appropriate group of patients and assess treatment efficacy.

A comparison of the outcomes of a novel technique of Mini-Incision and Self-Express (MISE) for breast abscess with the conventional techniques: a retrospective comparative cohort study.

Conventional techniques for treatment of breast abscess, such as incision and drainage (I&D) and needle aspiration, have disadvantages. The authors aimed to compare the outcomes of a novel technique of bedside mini-incision and self-express (MISE) for breast abscess with the conventional techniques. Methods: Patients with a pathologically confirmed breast abscess were retrospectively identified. Patients with mastitis, granulomatous mastitis, breast fillers with infection, ruptured abscess prior to intervention, other interventions or bilateral breast infection were excluded. Data collected included patient demographics, radiological features such as size and number of abscess, treatment modality, microbiological results and clinical outcomes. These outcomes were then compared between the patients with MISE, I&D and needle aspiration. Results: Twenty-one patients were included. The mean age was 31.5 years old (range: 18-48). Mean abscess size was 57.4 mm (range: 24-126). 5 (23.8%), 11 (52.4%) and 5 (23.8%) had MISE, needle aspiration and I&D, respectively. Average duration of antibiotics was 1.8, 3.9 and 2.6 weeks for MISE, needle aspiration and I&D groups, respectively, which was statistically significant after adjusting for confounders (P=0.024). Mean duration of recovery was 2.8, 7.8 and 6.2 weeks for the MISE, needle aspiration and I&D groups, respectively (P=0.027), after adjusting for confounders. Conclusion: MISE, in suitable patients, results in shorter recovery time and lesser antibiotics usage, compared with the conventional techniques.

Primary Eccrine Porocarcinoma of the Breast: A Case Report and Review of Literature.

Eccrine porocarcinoma (EPC) is a rare cutaneous neoplasm, with less than 500 reported cases worldwide since it was first described in 1963. EPC tends to affect the elderly and most commonly affects the head and neck. The mainstay of EPC treatment is surgery, with lymphadenectomy in the case of nodal involvement or presence of unfavourable characteristics. No evidence exists to guide the use of adjuvant chemotherapy or radiation. EPC is prone to misdiagnosis given its multiple clinical and histopathological mimics, especially in uncommon sites of presentation such as the breast. Herein, we report the case of a 59-year-old woman who presented with a left breast skin lump. The biopsied specimen revealed an infiltrative carcinoma involving the dermis and epidermis with positive IHC staining for P63 and CK5/6 and negative staining for ER, PR, and HER2. The tumour was resected and diagnosed as EPC with atypical features as overlapping characteristics of squamous cell carcinoma (SCC) were detected on histopathological analysis. In our case, a simple mastectomy with broad margins and axillary lymph node dissection with adjuvant radiotherapy to a dose of 60 Gy failed to achieve loco-regional control with nodal recurrence occurring 4 months postsurgery-a testament to the aggressive course of this rare malignancy.

Effect of pregnancy and lactation on a benign phyllodes tumour.

Phyllodes tumours occurring in pregnancy are very rare. While most cases presented as rapidly enlarging masses, we present a benign phyllodes tumour which had the most growth in the first half of pregnancy followed by gradual growth in the latter half of pregnancy and lactation, as characterised on ultrasound imaging. This is the first report, to the best of our knowledge, which has objective measurements of the lesion before, during and after pregnancy. It also highlighted the need for a vigilant approach to fibroepithelial lesions in pregnancy, instead of attributing the growth of these lesions solely to hormonal changes.

Genetic differences between benign phyllodes tumors and fibroadenomas revealed through targeted next generation sequencing.

Breast fibroepithelial lesions are biphasic tumors which comprise the common benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). This study analyzed 262 (42%) conventional FAs, 45 (7%) cellular FAs, and 321 (51%) benign PTs contributed by the International Fibroepithelial Consortium, using a previously curated 16 gene panel. Benign PTs were found to possess a higher number of mutations, and higher rates of cancer driver gene alterations than both groups of FAs, in particular MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR. Cases with MED12 mutations were also more likely to have TERT promoter, RARA, SETD2, and EGFR. There were no significant differences detected between conventional FAs and cellular FAs, except for PIK3CA and MAP3K1. TERT promoter alterations were most optimal in discriminating between FAs and benign PTs. Our study affirms the role of sequencing and key mutations that may assist in refining diagnoses of these lesions.

The Impact of Radiotherapy and Histological Risk Factors on Outcomes in Malignant Phyllodes Tumors.

PURPOSE: Breast phyllodes tumors (PT) are classified into benign, borderline, and malignant grades based on histopathologic characteristics. Specific to malignant PT (MPT), surgery is the mainstay yet relapse rates are high and knowledge gaps in the literature exist regarding adjuvant radiotherapy (RT). We aimed to investigate the outcomes of patients with MPT treated in a tertiary Asian institution. METHODS AND MATERIALS: Patients with nonmetastatic MPT treated from February 1992 to June 2019 were analyzed retrospectively. RT details and relapse fields were studied. Outcomes of patients with and without RT were compared and hazard ratios were calculated using Cox proportional hazard test. Multivariable analysis was performed. RESULTS: Twenty-two of 89 patients received adjuvant RT and the median dose was 60 Gy. In the no-RT group, 4 patients received RT on relapse and had no further recurrences; a further 2 received RT for fungating relapses with good symptomatic relief. RT was only increasingly prescribed after 2004. Median follow-up in the RT group was 3.31 years, compared with 6.17 years in the no-RT group. In the RT group, 15 patients (68.2%) underwent mastectomy, versus 39 (58.2%) in the no-RT group. One patient in the RT group developed an infield local relapse, compared with 21 of 67 patients in the no-RT group. Multivariate model showed that RT decreased risk of locoregional failure (hazard ratio 0.12, 95% confidence interval [CI] 0.02-0.92, P = .04). Three-year locoregional recurrence-free survival was higher in the RT group, 92.3% (95% CI, 78.9-100) versus 73.3% (95% CI, 63.1-85.1) in the no-RT group (P = .03). There were no differences in 3-year survival. CONCLUSIONS: We recommend that adjuvant radiotherapy be discussed for malignant PT for local control, even after mastectomy.

Would Removal of All Ultrasound Abnormal Metastatic Lymph Nodes Without Sentinel Lymph Node Biopsy Be Accurate in Patients with Breast Cancer with Neoadjuvant Chemotherapy?

LESSONS LEARNED: Removal of sonographically abnormal (up to 3) metastatic clipped nodes, without sentinel lymph node biopsy, could accurately predict axillary status in breast cancer patients receiving neoadjuvant chemotherapy. ypT and the first clipped node status were statistically significant factors for nodal pathologic complete response. This novel approach requires validation in larger studies. BACKGROUND: In patients who have node-positive breast cancer, neoadjuvant chemotherapy could result in nodal pathologic complete response (pCR) and avoid an axillary lymph node dissection (ALND). Axillary staging, in such cases, can be performed using targeted axillary dissection (TAD) with a low false negative rate. However, identification of sentinel lymph nodes (SLNs) after chemotherapy can be difficult, and currently, it is the standard to remove only one clipped node in TAD. We aimed to determine if removal of all sonographically abnormal metastatic clipped nodes, without SLN biopsy, could accurately predict the axillary status post neoadjuvant chemotherapy. METHODS: Patients with breast cancer with one to three sonographically abnormal metastatic axillary nodes were prospectively recruited. Each abnormal node had histology and clip insertion before neoadjuvant chemotherapy. After chemotherapy, the patients underwent removal of clipped nodes using the Skin Mark clipped Axillary nodes Removal Technique (SMART) and ALND. RESULTS: Fourteen patients were recruited, having a total of 21 sonographically abnormal metastatic nodes, with nine, three, and two patients having 1, 2, and 3 malignant nodes clipped, respectively. Mean age was 55.5 years; 92.9% and 57.1% of patients had invasive ductal carcinoma and grade III tumors, respectively; and 35.7% patients achieved nodal pCR. The first clipped node predicted the axillary status with a false negative rate of 7.1%. Adding to this another second clipped node, the false negative rate was 0%. Pathologic tumor staging after neoadjuvant chemotherapy (ypT) (p = .0390) and the first clipped node pathological response status (p = .0030) were statistically significant predictors for nodal pCR. CONCLUSION: Removal of sonographically abnormal metastatic clipped nodes using SMART, without sentinel lymph node biopsy, could accurately predict axillary status. This finding needs validation in larger studies.

Initial results of a novel technique of clipped node localization in breast cancer patients postneoadjuvant chemotherapy: Skin Mark clipped Axillary nodes Removal Technique (SMART trial).

PURPOSE: Removal of clipped nodes can improve sentinel node biopsy accuracy in breast cancer patients post neoadjuvant chemotherapy (NACT). However, the current methods of clipped node localization have limitations. We evaluated the feasibility of a novel clipped node localization and removal technique by preoperative skin marking of clipped nodes and removal by the Skin Mark clipped Axillary nodes Removal Technique (SMART), with the secondary aim of assessing the ultrasound visibility of the various clips in the axillary nodes after NACT. METHODS: Invasive breast cancer patients with histologically metastatic axillary nodes, going for NACT, and ≤3 sonographically abnormal axillary nodes were recruited. All abnormal nodes had clips inserted. Patients with M1 disease were excluded. Post-NACT, patients underwent SMART and axillary lymph node dissection. Specimen radiography and pathological analyses were performed to confirm the clipped node presence. Success, complication rates of SMART, and ultrasound visibility of the various clips were assessed. RESULTS: Twenty-five clipped nodes in 14 patients underwent SMART without complications. The UltraCor Twirl, hydroMARK, UltraClip Dual Trigger, and UltraClip were removed in 13/13 (100%), 7/9 (77.8%), 1/2 (50.0%), and 0/1 (0%), respectively (P = .0103) with UltraCor Twirl having the best ultrasound visibility and removal rate. Removal of three clipped nodes in the same patient (P = .0010) and deeply seated clipped nodes (P = .0167) were associated with SMART failure. CONCLUSION: Skin Mark clipped Axillary nodes Removal Technique is feasible for removing clipped nodes post-NACT, with 100% observed success rate, using the UltraCor Twirl marker in patients with <3 not deeply seated clipped nodes. Larger studies are needed for validation.

Comparing the Diagnostic Outcomes of Staining Various Breast Lesions with Either Anti-CK 5/6 or Anti-CK 5.

BACKGROUND AND OBJECTIVE: Anti-CK5/6 monoclonal antibodies have an established role in breast disease diagnosis. Anti-CK5 monoclonal antibodies have recently become commercially available. There has been growing interest in the staining characteristics of anti-CK5 and its potential diagnostic role in place of anti-CK5/6. We aim to compare and contrast the staining characteristics of anti-CK5/6 vs anti-CK5. MATERIAL AND METHODS: 58 tissue blocks containing 122 different lesions were selected from tissue archives. Two specimens (groups) were taken from each lesion One (group) was stained with anti-CK5 and the other (group) with anti-CK5/6 monoclonal antibodies, using the Streptavidin-biotin immuno-peroxidase method. The two groups of slides were compared and contrasted for lesion staining pattern and for intensity, using light microscopy. RESULTS: Results showed that the diagnostic staining pattern was exactly the same in both anti-CK5 and anti-CK5/6 groups, and also showed that anti-CK5, stained most of the lesions more intensely than anti-CK5/6. CONCLUSION: Anti-CK5 performed at least as well (for lesion-pattern staining), and better (for lesion staining intensity) than did anti-CK5/6 in the diagnosis of a wide range of breast tissues and lesions. It may be justified to safely replace anti-CK5/6 with anti-CK5 in future routine clinical use, with resultant diagnostic and economic benefits.

Genomic characterisation of breast fibroepithelial lesions in an international cohort.

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Granulomatous Mastitis and Factors Associated with Recurrence: An 11-Year Single-Centre Study of 113 Patients in Singapore.

BACKGROUND: Granulomatous mastitis (GM) is an inflammatory breast disease of unknown aetiology. It poses diagnostic and therapeutic challenges with myriad forms of clinical presentation, varying results to treatments and propensity to recur. This study aims to look at clinical and treatment factors that predispose to recurrence of GM. METHODS: We performed a retrospective review of 113 patients in our unit with histologically proven GM from 2006 to 2016. Demographic, clinical, treatment and outcomes data were collected and analysed. RESULTS: Eighty-nine patients were treated with antibiotics (78.8%), 79 (69.9%) with steroids and 23 (20.4%) patients underwent surgery. Twenty (17.7%) patients had recurrence. Patients who presented with inflammatory signs and symptoms had increased odds of having subsequent recurrence: skin changes (1.50), pain (2.00), fistula (4.39) and antibiotic treatment (6.65). Four patients (20%) with recurrence had positive bacterial cultures. All 4 grew Corynebacterium. Patients with Corynebacterium infection had a 2.64 times higher risk of recurrence. Surgery did not preclude recurrence. There was a 70% (7/10) penicillin resistance rate in our patients with positive cultures for Corynebacterium. CONCLUSION: Initial presentation with inflammatory signs and symptoms may confer increased risk of recurrence, warranting closer monitoring. Corynebacterium infection may play a part as a causative factor and risk factor for recurrence. Non-penicillin antibiotics should be considered as first-line antibiotics for patients presenting with inflammatory changes. Further prospective studies with larger patient populations might reveal information on the aetiology of GM and result in the development of a more standardized and effective treatment regimen.

Breast Microcalcifications as the Only Imaging Manifestation of Metastatic Serous Peritoneal Adenocarcinoma in the Breast.

We present a case of a 65 year old female with newly diagnosed primary peritoneal serous carcinoma who was found to have indeterminate segmental microcalcifications in the right upper outer quadrant with a mildly enlarged right axillary node on mammogram. There was no associated breast mass on ultrasound. Core biopsy of the right axillary lymph node and right upper outer quadrant breast microcalcifications confirmed the presence of breast metastases at both sites from primary peritoneal serous carcinoma. This case highlights the importance of histopathological correlation of any breast and axillary abnormalities in patient with primary extramammary malignancy. Imaging features of metastatic lesions to the breast are also reviewed.

Elevated WBP2 Expression in HER2-positive Breast Cancers Correlates with Sensitivity to Trastuzumab-based Neoadjuvant Therapy: A Retrospective and Multicentric Study.

PURPOSE: Trastuzumab-based chemotherapy has shown remarkable clinical benefits for patients with HER2-positive breast cancer. However, treatment regimens involving trastuzumab had little or no effect for a subset of patients. Preliminary studies revealed WW-binding protein 2 (WBP2), an oncogenic transcription coactivator, to be coamplified with HER2 in 36% of HER2-positive breast cancers. We hypothesize that WBP2 regulates and correlates with the response of HER2-positive breast cancer to trastuzumab. EXPERIMENTAL DESIGN: The coexpression of WBP2 and HER2 in breast tumors was validated using IHC. The role and mechanism of WBP2 in regulating breast cancer response to trastuzumab was elucidated using in vitro, patient-derived xenograft and murine xenograft models. A multicenter retrospective study involving 143 patients given neoadjuvant trastuzumab-based chemotherapy was conducted to determine whether WBP2 expression correlates with pathologic complete response (pCR). RESULTS: Elevated expression of WBP2 significantly enhanced breast cancer's response to trastuzumab by augmenting trastuzumab-induced HER2 downregulation and cell-cycle arrest via inhibition of cyclin D expression. High level of WBP2 correlated with better pCR (67.19%) compared with low WBP2 level (26.58%). The highest response was observed in subgroups of patients with high WBP2-expressing tumors also aged below 50 years (77.78%) or were premenopausal in status (73.33%). Retrospectively, WBP2 demonstrated sensitivity of 80% to 81% and specificity of 76.5% to 80% in discriminating between patients showing pCR and non-pCR. CONCLUSIONS: WBP2 expression correlates with the response of HER2-positive breast cancer to trastuzumab-based neoadjuvant chemotherapy.

Diagnostic dilemma of micropapillary variant of mucinous breast cancer.

An elderly woman presented with an enlarging left breast lump. Breast imaging revealed a large suspicious mass associated with cystic components. Core biopsy however was non-diagnostic and only revealed necrotic papillary tissue. The patient then underwent excision of the lesion that revealed a large area of intracystic papillary ductal carcinoma in situ with a focus of micropapillary variant of mucinous cancer. This case describes how this rare subtype could present as necrotic papillary tissue on core biopsy, resulting in a diagnostic dilemma, which had not been previously reported. A literature review of this rare subtype was performed too.

Natural history of luminal A breast invasive ductal carcinoma in an elderly.

An elderly woman, with no clinically palpable breast lump, presented with an initially benign-appearing lesion on ultrasound. She was followed up to reveal the natural history of luminal A breast cancer.