Granular Cell Tumor Mimicking Breast Carcinoma: A Report of Two Cases.

Granular cell tumor (GCT) of the breast is a rare neoplasm that can mimic the clinical and radiological features of breast carcinoma. This paper presents two case reports - a rare male case and a more common female case - to underline the diagnostic challenges posed by GCT in the breast. The male patient was initially suspected of having a breast tumor based on mammography and ultrasound findings. The female patient also exhibited radiological signs suggestive of breast cancer. In both cases, the mammograms showed irregular lesions, while ultrasounds revealed solid masses with posterior shadowing and echogenic halos, mimicking carcinoma. Dynamic contrast-enhanced magnetic resonance imaging (MRI) suggested benign patterns in both cases, but only histopathologic examination post-core needle biopsy confirmed the diagnosis of GCT. These cases highlight the variability of GCT imaging presentations and the potential for misdiagnosis as breast carcinoma. The tumors exhibited distinct histopathological features, such as large polygonal cells with granular eosinophilic cytoplasm and S100 protein, differentiating them from breast carcinoma. However, imaging alone proved insufficient for diagnosis, emphasizing the need for histopathologic confirmation. The report discusses the importance of including GCT in differential diagnoses and utilizing core needle biopsy for accurate evaluation. Both cases had no recurrence during follow-up after wide resection, indicating a favorable prognosis for GCT when properly managed.

Granulocyte-Colony Stimulating Factor (G-CSF)-Induced Aortitis: A Case Report.

Pegylated granulocyte colony-stimulating factor (G-CSF), commonly used in chemotherapy-induced neutropenia, has been associated with rare instances of aortitis. This study describes a 67-year-old female patient with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2-positive breast cancer, undergoing chemotherapy with an epirubicin/cyclophosphamide (EC) regimen (epirubicin, cyclophosphamide) and pegylated G-CSF for neutropenia prophylaxis. Post-treatment, she developed symptoms including intermittent fever and severe arthralgia. Laboratory tests revealed an elevated white blood cell count, C-reactive protein levels, and erythrocyte sedimentation rate, while a computed tomography scan showed thickening in the aortic arch and descending aorta. Given the clinical presentation and exclusion of other potential causes, pegylated G-CSF-induced aortitis was suspected. The patient's symptoms improved significantly following the cessation of pegylated G-CSF, aiding in the differentiation from other types of aortitis. This study highlights the importance of considering pegylated G-CSF as a potential cause of aortitis in patients presenting with unexplained symptoms of fever and inflammation after chemotherapy. The rapid improvement upon discontinuation of the drug is a key feature distinguishing it from other aortitis causes. In conclusion, while rare, aortitis should be considered in the differential diagnosis of patients treated with pegylated G-CSF who exhibit relevant clinical symptoms. Early detection and management, including the discontinuation of the causative agent, are crucial for patient recovery and prognosis.

Risk factors for late recurrence and postrelapse survival in estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative breast cancer after 5 years of endocrine therapy.

It is unclear which patients with ER-positive, HER2-negative breast cancer benefit from extended endocrine therapy beyond 5 years. Prognostic factors for late-recurring breast cancer postrelapse survival have been reported. We retrospectively analyzed data from 892 patients with ER-positive and HER2-negative invasive breast cancer who were disease-free after completing a 5-year adjuvant endocrine therapy. Patients were then classified as high-risk (positive lymph nodes, large tumor size, high tumor grade) or low-risk. High-risk patients were divided into extended endocrine therapy and stop groups. Comparisons were made using propensity score matching, and the benefits of extended endocrine therapy for high-risk patients and prognostic factors for postrelapse survival were assessed. The high- and low-risk groups comprised 444 and 448 patients, respectively. The 10-year distant disease-free survival (DDFS) rates were 96.3 % (95 % confidence interval [CI] 0.912-0.985) and 86.5 % (95 % CI 0.798-0911) in the extended and stop groups, respectively (P = 0.00382). Cox proportional hazards model revealed that extended endocrine therapy promoted greater reduction in distant metastasis risk than 5-year endocrine therapy in high-risk populations (hazard ratio [HR] 0.27; 95 % CI 0.11-0.68; P = 0.0054). Postrelapse survival was significantly different in patients with DDFS ≥7 years (HR 0.24; 95 % CI 0.072-0.81; P = 0.021) and those with better response to first-line treatment (HR 0.072; 95 % CI, 0.058-0.90; P = 0.041). Patients with risk factors for late recurrence should be considered for extended endocrine therapy. Longer DDFS and response to first-line treatment may be a prognostic factor for postrelapse survival after late recurrence.

Negative progesterone receptor status correlates with increased risk of breast cancer recurrence in luminal B HER2-positive and -negative subtypes.

OBJECTIVES: The prognostic significance of the progesterone receptor (PR) has been widely investigated in luminal A and luminal B [human epidermal growth factor receptor 2 (HER2)-] breast cancer subtypes, both of which are estrogen receptor (ER)-positive and HER2-negative. In contrast, few studies have focused on PR status in luminal B (HER2+) tumors. The aim of this study was to evaluate the impact of positive PR status on outcomes in patients with luminal B (HER2-) or luminal B (HER2+) breast cancer. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in 469 breast cancer patients with the luminal B (HER2-) or luminal B (HER2+) subtype. The relationship between PR and HER2 status was also assessed. RESULTS: Of 387 luminal B (HER2-) and 82 luminal B (HER2+) cancers, PR+ was significantly more frequent in the former than the latter (86.3% vs. 61.0%, respectively; P<0.001). In univariate analysis, PR was identified as a significant favorable prognostic factor for distant disease-free survival and overall survival in both subtypes, but in multivariate analysis PR was not an independent prognostic factor. CONCLUSIONS: After patients with luminal B subtype were divided into two subgroups according to HER2 status, there was evidence of a relatively good prognosis in the PR+ subgroup. Further studies with a larger number of patients are recommended to validate these findings.

Upregulation of CIP2A in estrogen depletion-resistant breast cancer cells treated with low-dose everolimus.

Everolimus (EVE), an inhibitor of mammalian target of rapamycin, is an emerging second-line therapeutic option for hormone therapy-resistant breast cancers. However, some patients do not respond to EVE, whereas in others it exacerbates the disease. Cellular inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that can promote cancer cell growth and apoptosis resistance. Although CIP2A is upregulated in hormone-related cancers, such as breast cancer, little is known about potential anti-tumor effects of downregulating CIP2A. As a model to study the resistance of breast cancer cells to hormone treatment, we previously established clones of long-term estrogen depletion-resistant MCF-7 (LTED) cells. Here, we selected three clones highly responsive to EVE and three clones poorly responsive to EVE. When cells were treated with EVE, CIP2A mRNA expression was decreased in highly responsive EVE clones (DC-cells) whereas it was increased in poorly responsive EVE clones (IC-cells). Using Kaplan-Meier survival plots, we report that high expression of CIP2A was associated with significantly reduced overall survival in patients with luminal A breast cancer. In IC-cells, cell growth was enhanced upon EVE treatment whereas an EVE range of 0.1-100 nm decreased growth in DC-cells. The mRNA expression of genes involved in epithelial-mesenchymal transition (EMT) such as CDH1, CLDN3, and CK19 was significantly decreased in IC-cells, but remained unchanged in DC-cells. These findings highlight a relationship between CIP2A and EMT in the intrinsic resistance of hormone therapy-resistant breast cancers to EVE.

Inverse correlation between Ki67 expression as a continuous variable and outcomes in luminal HER2-negative breast cancer.

OBJECTIVES: Few studies to date have investigated the prognostic significance of Ki67 expression as a continuous variable in breast cancer. This study aimed to evaluate the impact of Ki67 expression as a dichotomous or continuous variable on outcomes in estrogen receptor (ER)+ and human epidermal growth factor receptor 2 (HER2)- breast cancer. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in retrospective data from 794 patients with ER+/HER2- breast cancer. We assessed the relationship between outcomes and two Ki67 cutoffs, 14% and 20%, and the Ki67 labeling index as a continuous variable. RESULTS: In univariate analysis, T stage, lymph node involvement, histological grade, progesterone receptor status, and Ki67 expression at the two cutoffs and as a continuous variable were identified as significant prognostic factors for distant disease-free survival (DDFS) and overall survival (OS). There were no statistical differences in DDFS and OS between women with Ki67 expression of <14% and 14-<20%. Multivariate analysis showed that Ki67 expression ≥20% was an independent prognostic indicator for DDFS. Regarding the risk of distant metastasis, the 20% cutoff was more reliable than 14%. We also found that Ki67 expression as a continuous variable was an independent prognostic factor for DDFS and OS in multivariate analyses. CONCLUSIONS: High Ki67 expression is associated with a survival disadvantage in patients with ER+/HER2- breast cancer, indicating that these patients might have a higher risk of recurrence after primary treatment and might therefore benefit from individualized treatment.

Differences in clinicopathologic features and subtype distribution of invasive breast cancer between women older and younger than 40 years.

OBJECTIVES: We investigated and compared clinicopathologic features and subtype distribution of invasive breast cancer among women <40 and ≥40 years of age. METHODS: We retrospectively compared clinicopathologic characteristics and subtype distribution of invasive breast cancer in women <40 and ≥40 years of age, in a cohort of 1,130 patients. Subtypes included luminal A (positive for hormone receptors [HR]-estrogen receptor [ER] and/or progesterone receptor [PR]-and negative for human epidermal growth factor receptor 2 [HER2] with low Ki67), luminal B (HER2-) (HR+/HER2-/Ki67High), luminal B (HER2+) (HR+/HER2+), HER2-overexpressing (HR-/HER2+), and triple negative (ER-/PR-/HER2-). RESULTS: Breast cancers in younger women had unfavorable clinicopathologic characteristics, including larger tumors and more frequent node involvement. Subtypes among the 1,130 tumors were luminal A: 36.4%, luminal B (HER2-): 35.0%, luminal B (HER2+): 7.5%, HER2-overexpressing: 7.1%, and triple negative: 14.0%. The age groups significantly differed in subtype distribution (P<0.001). Luminal A subtype was more common in the older group (38.5%) than the younger group (16.2%), and luminal B (HER2-) was more common in the younger group (52.2%) than in the older group (33.2%; P<0.001). CONCLUSIONS: Breast cancers in women younger than 40 years have unfavorable clinicopathologic characteristics and are more likely to be luminal B (HER2-) and less likely to be luminal A than breast cancers in older women.

Forskolin increases the effect of everolimus on aromatase inhibitor-resistant breast cancer cells.

Aromatase inhibitor (AI) resistance is a major obstacle in the treatment of estrogen receptor-positive breast cancer. Everolimus (EVE) ameliorates AI-resistant breast cancer and is therefore used in cancer treatment. However, some patients show resistance to EVE. Here, we used 30 clones of long-term estrogen-deprived (LTED) MCF-7 cells as a model of AI-resistant breast cancer. We examined changes in protein phosphatase type 2A (PP2A) and cancerous inhibitor of PP2A (CIP2A), a negative regulator of PP2A, in LTED cells treated with EVE. In LTED cells with high sensitivity to EVE, CIP2A expression decreased at low EVE concentrations; however, in LTED cells poorly sensitive to EVE, CIP2A and PP2A did not change upon exposure to EVE. Therefore, we hypothesized that there is a relation between expression of CIP2A and sensitivity to EVE. Knockdown of CIP2A increased the sensitivity to EVE in three clones poorly sensitive to EVE. Additionally, we found that treatment with FSK, which activates PP2A, increased the sensitivity of the cells to EVE. Our data point to CIP2A and PP2A as novel therapeutic targets for AI-resistant breast cancer.

A Hypoglycemia-inducing Giant Borderline Phyllodes Tumor Secreting High-molecular-weight Insulin-Like Growth Factor II: Immunohistochemistry and a Western Blot Analysis.

A 50-year-old woman with a large right breast mass was emergently hospitalized for generalized weakness and fatigue. A histological examination of tumor biopsy specimens revealed a phyllodes tumor (PT). She suddenly lost consciousness due to severe hypoglycemia. Non-islet cell tumor hypoglycemia (NICTH) due to the PT was suspected. The tumor was emergently resected. A histological examination revealed a borderline PT. The patient recovered from the hypoglycemic episode. High-molecular-weight insulin-like growth factor II was detected in serum that had been collected preoperatively and in the tumor tissue, but not in serum that had been collected postoperatively. We herein present a case of a borderline PT with NICTH.

Estradiol suppresses phosphorylation of ERα serine 167 through upregulation of PP2A in breast cancer cells.

Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167. The tumor suppressor serine/threonine-protein phosphatase 2A (PP2A) regulates the phosphatidylinositol 3-kinase/RAC serine/threonine-protein kinase signaling pathway. A previous study indicated that PP2A inhibition decreased ERα Ser167 phosphorylation and estradiol (E2)-independent cell growth. The present study investigated the potential relevance of PP2A in E2 deprivation-resistant MCF-7 cells. E2 depletion reduced the susceptibility of MCF-7 cells to inhibitors of mechanistic target of rapamycin (mTOR) and significantly increased ERα Ser167 phosphorylation and decreased expression of PP2A. Conversely, long-term E2-deprived (LTED) MCF-7 cells, a model of AI-resistant breast cancer, exhibited decreased ERα Ser167 phosphorylation and further upregulation of PP2A in E2-containing medium. The PP2A activator forskolin (FSK) significantly inhibited LTED cell proliferation by increasing the effect of everolimus (Eve), an mTOR inhibitor. In summary, the present study provides further evidence that PP2A represents a therapeutic target for AI-resistant breast cancer.

Pneumatosis cystoides intestinalis associated with massive free air mimicking perforated diffuse peritonitis.

While pneumatosis cystoides intestinalis (PCI) is a rare disease entity associated with a wide variety of gastrointestinal and non-gastrointestinal disorders, PCI associated with massive intra- and retroperitoneal free air is extremely uncommon, and is difficult to diagnose differentially from perforated peritonitis. We present two cases of PCI associated with massive peritoneal free air and/or retroperitoneal air that mimicked perforated peritonitis. These cases highlight the clinical importance of PCI that mimics perforated peritonitis, which requires emergency surgery. Preoperative imaging modalities and diagnostic laparoscopy are useful to make an accurate diagnosis.