Adenomyoepithelioma of the Breast: Radiologic-Pathologic Correlation and Management.

Adenomyoepithelioma (AME) is a rare, usually benign breast neoplasm with low potential for malignant transformation. Imaging features are nonspecific and overlap with other benign and malignant breast lesions. On mammography, AME most often presents as a mass, usually oval in shape, with variable reported margins. Less commonly, AME can present mammographically as an asymmetry or can be mammographically occult. Associated calcifications are uncommon. On US, AME is usually seen as a hypoechoic oval mass, but it can also manifest as a complex cystic and solid mass. On US, the majority of AME have noncircumscribed margins (indistinct, angular, or microlobulated). Internal vascularity is usually present, and posterior enhancement can be seen. Although there is limited literature on MRI features, the most frequent finding is an irregular mass with washout kinetics; T2 hyperintensity can be observed. These nonspecific and often suspicious imaging features usually merit biopsy. On histologic analysis, AME is characterized by a biphasic proliferation of myoepithelial and epithelial cells. Pathologic diagnosis can be difficult due to the variety of histologic features of AME and heterogeneity in these tumors, especially when sampling is limited, such as in core needle biopsies. Wide local surgical excision of AME is recommended due to potential for recurrence and malignant transformation.

Ductal Carcinoma Arising in a Squamous Epithelial Inclusion Cyst within an Axillary Lymph Node: A Challenging Nodal Metastasis.

Introduction. Assessment of axillary lymph nodes in breast carcinoma is an important part of staging to guide appropriate clinical management. Lymph node inclusions of different types, including nevoid, squamous, and glandular, are rare but have been reported in multiple different anatomic locations including the axilla. These can result in diagnostic challenges and pose risks of misdiagnoses. Rarely, malignancies may arise intrinsic to otherwise incidental benign nodal inclusions. Case Presentation. We report a case of ductal carcinoma diagnosed within a squamous epithelial inclusion cyst within an axillary lymph node in a patient with pure ductal carcinoma in situ (DCIS) of the ipsilateral right breast. To our knowledge, this is the fifth report in the literature of breast carcinoma confirmed within an axillary inclusion in a patient with pure DCIS. Evaluation of the primary DCIS and lymph node inclusions, by routine and immunohistochemical stains, was performed for assessment. Discussion. The presence of lymph node inclusions can pose a challenge in assessment of benignity and malignancy, on frozen and permanent histologic sections. Pathologists should carefully evaluate lymph node inclusions to ensure that intrinsic malignancies are not missed within rare otherwise benign appearing incidental epithelial rests.

Allowing Surgical Pathology Fellows to Release Preliminary Reports Increases Learner Independence and Satisfaction.

CONTEXT.­: Progressive independence in medicine is critical to building confidence and decisiveness in trainees. However, this can be difficult to accomplish in the strict regulatory environment of pathology. OBJECTIVE.­: To pilot and adopt a process whereby surgical pathology fellows independently manage a subset of cases and release preliminary reports. DESIGN.­: Upon program approval, board-certified surgical pathology fellows were eligible for preliminary report sign-out at their discretion. Eligible cases were sent from outside institutions for confirmatory review. Preliminary reports were viewable in the electronic medical record. Safety measures were used to ensure timely release of final reports by attending pathologists. RESULTS.­: Fellows participating in the pilot (n = 4) released 59 preliminary reports out of 101 cases reviewed (58%), with 1 potentially significant discrepancy between preliminary and final report. Turnaround time was not affected. The process was endorsed by all participants and adopted as standard practice. During the first year, eligible fellows (n = 8) released 123 preliminary reports out of 1260 cases reviewed (9.8%). There were no major diagnostic discrepancies and no effects on turnaround time. The number of preliminary reports released by each fellow was variable (range, 2-48; median, 8), likely a reflection of both external factors (number of trainees on service, volume) and trainee-specific factors (confidence, efficiency). CONCLUSIONS.­: Fellows showed good judgment when independently managing cases, with just 1 potentially significant discrepancy out of 182 cases (<1%). No patients were adversely impacted. Use of this process varied widely among fellows and may require closer monitoring and encouragement for fellows who are tentative about releasing preliminary reports.

Eosinophilic mastitis mimicking a developing asymmetry.

Eosinophilic mastitis is a very rare form of mastitis with few reported cases in the literature. This is a case of eosinophilic mastitis in a 48-year-old woman which presented as a screen detected right breast developing asymmetry. No sonographic abnormalities were visualized on diagnostic workup, and subsequent tomosynthesis-guided biopsy was performed. Knowledge of this rare entity is helpful in the radiologic-pathologic correlation, diagnosis, and clinical management of future cases.

Pictorial Review of Common and Uncommon Pediatric Breast Lesions.

Breast masses in children and adolescents are uncommon, and the spectrum of pediatric breast masses is predominantly benign and different from that in adults. Knowledge of the clinical presentation and imaging features of the various stages of normal development and mass-forming lesions in the pediatric breast can guide a tailored imaging approach and help the radiologist make a definitive diagnosis. Breast development begins during fetal gestation along the embryologic milk lines and continues through puberty as the breast matures through the Tanner stages of development. Normal and developmental variants and benign neoplastic and nonneoplastic lesions in the pediatric breast are common causes of concern. Malignant breast masses in children are rare and are more often due to metastasis than primary breast cancer. When clinically warranted, US is the mainstay for imaging the pediatric breast and requires careful correlation of sonographic findings with patient age and history. Breast MRI can be used to further characterize lesions and evaluate the extent of disease. Biopsy should be considered only for suspicious findings and must be weighed against the risk of iatrogenic injury to the developing breast. Given that the majority of mass-forming lesions in the pediatric breast are benign, the diagnostic and management approach should emphasize "first do no harm." Knowledge of the imaging appearance of normal breast development and the spectrum of benign and malignant pediatric breast masses is necessary to make the correct diagnosis. © RSNA, 2022.

Lack of Clinical Value for Immunohistochemistry for Sentinel Lymph Node Assessment in Invasive Lobular Carcinoma.

BACKGROUND: The distinct histologic appearance of invasive lobular carcinoma (ILC) may pose diagnostic challenges for sentinel lymph node (SLN) analysis. We evaluated the impact of cytokeratin immunohistochemistry (IHC) on SLN assessment in ILC and its contribution to pathologic nodal upstaging. METHODS: We identified ILC patients treated with SLN surgery at our institution between September 2008 and August 2021. IHC for SLN assessment was employed at the discretion of the pathologist. Differences between groups evaluated with and without IHC were compared using Chi-square tests. RESULTS: Overall, 608 cases of ILC were identified in patients who underwent SLN surgery. IHC was used in 301 cases (49.5%) and was not associated with cT category, pT category, or tumor grade. Use of IHC increased detection of SLN+ disease when isolated tumor cells (ITCs) were included in the analysis (35.9% with IHC vs. 21.2% without IHC; p < 0.001). There was no effect on nodal upstaging to micrometastatic disease (pN1mi) or greater (21.9% with IHC vs. 21.2% without IHC; p = 0.82). IHC did not increase the number of positive SLNs detected (median 1 with and without IHC) nor did it increase axillary lymph node dissection (ALND) rates (11.6% with IHC vs. 15.3% without IHC; p = 0.18). CONCLUSION: IHC improved detection of pN0(i+) disease among ILC patients undergoing SLN surgery. IHC did not increase upstaging to pN1mi or higher categories of nodal disease, detection of a greater number of positive SLNs, or ALND rates. Our data suggest routine use of IHC for SLN assessment in ILC patients does not add clinical utility.

Local Recurrence of Invasive Secretory Breast Carcinoma in a Gravid Patient Post-Mastectomy.

This is a case of locally recurrent invasive secretory carcinoma of the breast during pregnancy, detected as a palpable mass in the reconstructed right breast of a 32-year-old female at 24 weeks gestation. The patient was initially diagnosed with secretory carcinoma 8 years prior, for which she underwent nipple sparing mastectomy followed by adjuvant chemotherapy and endocrine therapy. Due to pregnancy, the recurrence was treated initially with conservative excision alone, followed by definitive management postpartum which included wide local excision, sentinel lymph node biopsy and adjuvant chest wall radiation. Secretory carcinoma of the breast is a rare cancer with a predilection for young age and indolent course. This case report describes an unusual case of recurrent secretory carcinoma, of interest due to both its diagnosis during pregnancy, and its recurrence after nipple sparing mastectomy.

Imaging features of adenosquamous carcinoma of the breast - A rare variant of metaplastic breast carcinoma.

Adenosquamous carcinoma of the breast is a rare subtype of metaplastic carcinoma, which accounts for <1% of invasive breast malignancy. Metaplastic carcinoma is usually high grade and aggressive with typically reported benign imaging features when compared to invasive ductal carcinoma. However, the adenosquamous variant is a subtype with a more favorable prognosis. Within the literature, there is limited imaging description with case studies focusing on metaplastic carcinoma. Herein, we report seven cases of the adenosquamous subtype describing the imaging findings with correlation to clinical history and pathology. The majority of patients (n = 6) presented with palpable breast masses. One patient was identified through screening mammography. Mammographically (n = 6), tumors appeared as irregular masses. Sonographically (n = 7), tumors appeared as irregular masses ranging from solid to mixed solid/cystic masses. On MRI (n = 1), one tumor appeared as an irregular rim enhancing mass. FDG PET/CT (n = 2) and whole-body bone scan (n = 1) were also available for review. The majority of tumors were low-grade (n = 6) with only one high-grade tumor. This case series of seven patients demonstrated predominantly suspicious imaging features despite the majority being low-grade tumors.

Laboratory Medicine and Pathology Education During the COVID-19 Pandemic-Lessons Learned.

The rapidly spreading COVID-19 pandemic demanded immediate organizational pivots in departments of laboratory medicine and pathology, including development and implementation of severe acute respiratory syndrome coronavirus 2 diagnostics in the face of unprecedented supply chain shortages. Laboratory medicine and pathology educational programs were affected in numerous ways. Here, we overview the effects of COVID-19 on the large, academic Department of Laboratory Medicine and Pathology educational practice at Mayo Clinic, highlighting lessons learned for the post-pandemic era and planning for the possibility of a future pandemic.

Vulvar apocrine hidradenocarcinoma arising in a hidradenoma papilliferum-A case report.

Hidradenoma papilliferum (HP) is a benign adnexal neoplasm of the vulva that typically presents as a unilateral, flesh-colored papule in the labium majus in middle-aged Caucasian women. It is considered to be a close counterpart of the intraductal papilloma of the breast. Malignant transformation is rare with few reports in the literature. We present a case of vulvar mammary-type apocrine hidradenocarcinoma arising in an HP.

Tiger-Striped PASH: Recognition of a Unique Morphology Allows for a Zippered-Up Diagnosis of Pseudoangiomatous Stromal Hyperplasia of Breast.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is histologically characterized by anastomosing and slit-like spaces invested by collagenous stroma and lined by flattened, spindle cells. These clear spaces that may mimic microscopic vascular channels do not contain red blood cells. Immunohistochemistry (IHC) studies may also help to confirm a diagnosis of PASH, with the spindled cells marking positively with CD34 and PR while demonstrating no reactivity with more specific endothelial antigens such as CD31 and ERG. In the current case, a 39-year-old female was diagnosed with cellular PASH of the right breast with unique histological patterns showing "tiger-striped" and "zippered" histologies. To our knowledge, this is the first report of these unique variant PASH morphologies.

Cytomorphology of ciliated foregut cyst of the pancreas.

Ciliated foregut cysts are benign congenital lesions that are commonly found in the mediastinum but are rare in the retroperitoneum. So far only very few cases of ciliated foregut cyst found in the pancreas have been reported, and less with cytologic findings described. We report a case of ciliated foregut cyst in pancreas in an asymptomatic patient diagnosed on fine needle aspiration cytology. We also discuss the cytology features that would help with the diagnosis, and the differential diagnosis that should be considered.

Invasive Mammary Carcinoma With Mixed Invasive Papillary and Glycogen Rich Clear Cell Features.

Invasive papillary carcinoma (IPC) and glycogen-rich clear cell carcinoma (GRCCC) are rare primary breast carcinomas. IPC typically have favorable prognosis, whereas the prognosis of GRCCC is less established. We report a unique case of high-grade invasive mammary carcinoma with mixed IPC and GRCCC features. We review the imaging and pathologic features and discuss prognosis of these unusual breast cancer subtypes.

Activation of the cholinergic anti-inflammatory pathway by GTS-21 attenuates cisplatin-induced acute kidney injury in mice.

Acute kidney injury (AKI) is the most common side effect of cisplatin, a widely used chemotherapy drug. Although AKI occurs in up to one third of cancer patients receiving cisplatin, effective renal protective strategies are lacking. Cisplatin targets renal proximal tubular epithelial cells leading to inflammation, reactive oxygen species, tubular cell injury, and eventually cell death. The cholinergic anti-inflammatory pathway is a vagus nerve-mediated reflex that suppresses inflammation via α7 nicotinic acetylcholine receptors (α7nAChRs). Our previous studies demonstrated the renoprotective and anti-inflammatory effects of cholinergic agonists, including GTS-21. Therefore, we examined the effect of GTS-21 on cisplatin-induced AKI. Male C57BL/6 mice received either saline or GTS-21 (4mg/kg, i.p.) twice daily for 4 days before cisplatin and treatment continued through euthanasia; 3 days post-cisplatin mice were euthanized and analyzed for markers of renal injury. GTS-21 significantly reduced cisplatin-induced renal dysfunction and injury (p<0.05). GTS-21 significantly attenuated renal Ptgs2/COX-2 mRNA and IL-6, IL-1ß, and CXCL1 protein expression, as well as neutrophil infiltration after cisplatin. GTS-21 blunted cisplatin-induced renal ERK1/2 activation, as well as renal ATP depletion and apoptosis (p<0.05). GTS-21 suppressed the expression of CTR1, a cisplatin influx transporter and enhanced the expression of cisplatin efflux transporters MRP2, MRP4, and MRP6 (p<0.05). Using breast, colon, and lung cancer cell lines we showed that GTS-21 did not inhibit cisplatin's tumor cell killing activity. GTS-21 protects against cisplatin-AKI by attenuating renal inflammation, ATP depletion and apoptosis, as well as by decreasing renal cisplatin influx and increasing efflux, without impairing cisplatin-mediated tumor cell killing. Our results support further exploring the cholinergic anti-inflammatory pathway for preventing cisplatin-induced AKI.

Magnesium improves cisplatin-mediated tumor killing while protecting against cisplatin-induced nephrotoxicity.

Approximately 30% of all cancer patients treated with cisplatin, a widely used broad-spectrum chemotherapeutic agent, experience acute kidney injury (AKI). Almost all patients receiving cisplatin have magnesium (Mg) losses, which are proposed to aggravate AKI. Currently, there are no methods to successfully treat or prevent cisplatin-AKI. Whereas Mg supplementation has been shown to reduce AKI in experimental models and several small clinical trials, the effects of Mg status on tumor outcomes in immunocompetent tumor-bearing mice and humans have not been investigated. The purpose of this study was to further examine the effects of Mg deficiency (±Mg supplementation) on cisplatin-mediated AKI and tumor killing in immunocompetent mice bearing CT26 colon tumors. Using a model where cisplatin alone (20 mg/kg cumulative dose) produced minimal kidney injury, Mg deficiency significantly worsened cisplatin-mediated AKI, as determined by biochemical markers (blood urea nitrogen and plasma creatinine) and histological renal changes, as well as markers of renal oxidative stress, inflammation, and apoptosis. By contrast, Mg supplementation blocked cisplatin-induced kidney injury. Using LLC-PK1 renal epithelial cells, we observed that Mg deficiency or inhibition of Mg uptake significantly enhanced cisplatin-induced cytotoxicity, whereas Mg supplementation protected against cytotoxicity. However, neither Mg deficiency nor inhibition of Mg uptake impaired cisplatin-mediated killing of CT26 tumor cells in vitro. Mg deficiency was associated with significantly larger CT26 tumors in BALB/c mice when compared with normal-fed control mice, and Mg deficiency significantly reduced cisplatin-mediated tumor killing in vivo. Finally, Mg supplementation did not compromise cisplatin's anti-tumor efficacy in vivo.

Magnesium protects against cisplatin-induced acute kidney injury without compromising cisplatin-mediated killing of an ovarian tumor xenograft in mice.

Cisplatin, a commonly used chemotherapeutic for ovarian and other cancers, leads to hypomagnesemia in most patients and causes acute kidney injury (AKI) in 25-30% of patients. Previously, we showed that magnesium deficiency worsens cisplatin-induced AKI and magnesium replacement during cisplatin treatment protects against cisplatin-mediated AKI in non-tumor-bearing mice (Solanki MH, Chatterjee PK, Gupta M, Xue X, Plagov A, Metz MH, Mintz R, Singhal PC, Metz CN. Am J Physiol Renal Physiol 307: F369-F384, 2014). This study investigates the role of magnesium in cisplatin-induced AKI using a human ovarian tumor (A2780) xenograft model in mice and the effect of magnesium status on tumor growth and the chemotherapeutic efficacy of cisplatin in vivo. Tumor progression was unaffected by magnesium status in saline-treated mice. Cisplatin treatment reduced tumor growth in all mice, irrespective of magnesium status. In fact, cisplatin-treated magnesium-supplemented mice had reduced tumor growth after 3 wk compared with cisplatin-treated controls. While magnesium status did not interfere with tumor killing by cisplatin, it significantly affected renal function following cisplatin. Cisplatin-induced AKI was enhanced by magnesium deficiency, as evidenced by increased blood urea nitrogen, creatinine, and other markers of renal damage. This was accompanied by reduced renal mRNA expression of the cisplatin efflux transporter Abcc6. These effects were significantly reversed by magnesium replacement. On the contrary, magnesium status did not affect the mRNA expression of cisplatin uptake or efflux transporters by the tumors in vivo. Finally, magnesium deficiency enhanced platinum accumulation in the kidneys and renal epithelial cells, but not in the A2780 tumor cells. These findings demonstrate the renoprotective role of magnesium during cisplatin AKI, without compromising the chemotherapeutic efficacy of cisplatin in an ovarian tumor-bearing mouse model.

Omega-3 polyunsaturated fatty acids enhance cytokine production and oxidative stress in a mouse model of preterm labor.

OBJECTIVE: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy remains controversial. We sought to examine the effects of ω-3 PUFA on inflammation and oxidative stress in vitro and in vivo using a model of preterm labor. METHODS: In vivo. Female Swiss Webster mice were fed a normal diet or a 5% fish oil (FO) diet for 3 weeks then mated with normal-fed males. On gestational day 15, dams were injected with either saline (n=10 per group) or lipopolysaccharide (LPS, intrauterine) (n=10 per group). Maternal plasma, amniotic fluid, placentas, and uteri were collected 4 h later and assessed for cytokines; maternal plasma and amniotic fluids were analyzed for oxidative stress. In vitro. RAW264.7 mouse macrophage-like cells were treated with either: vehicle, H2O2, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) (0, 0.1-100 µM) and analyzed for oxidative stress. RESULTS: In vivo. Administration of the 5% FO diet enhanced LPS-induced cytokines in the placenta (P<0.05-0.01) and increased tumor necrosis factor-α in the uterus (P<0.05) and amniotic fluid (P<0.01) when compared to LPS-treated normal-fed animals. Maternal plasma obtained from FO-fed dams showed higher LPS-induced oxidative stress than control-fed animals (P<0.035). However, no differences in oxidative stress were observed in the amniotic fluid. In vitro. Treatment of macrophage-like cells with ω-3 PUFA significantly and dose-dependently increased oxidative stress (P<0.001-0.0001). CONCLUSIONS: Supplementation with FO for prior to and during pregnancy significantly increased LPS-induced inflammation in the amniotic fluid, uterus, and placenta and significantly increased maternal systemic oxidative stress in vivo. Likewise, DHA and EPA induced oxidative stress in macrophage-like cells in vitro.