Asumi Iesato

Breast metastases of gastric signet-ring cell carcinoma: a report of two cases and review of the literature.

It is occasionally difficult to diagnose breast metastasis of gastric carcinoma because of its rarity. However, to appropriately treat patients with breast tumors without delay, it is important to distinguish metastatic cancer from primary breast cancer. We report two cases of breast metastasis of gastric carcinoma and review the literature. The first case was a 41-year-old female diagnosed with bilateral pelvic tumors who visited the outpatient clinic because of pain and enlargement of both breasts. Ultrasonography showed diffuse hypoechoic lesions, which were enhanced on gadolinium-enhanced magnetic resonance imaging in the bilateral mammary gland. Core needle biopsy of the right breast revealed signet-ring cells, which were also identified in the resected bilateral pelvic tumors. Subsequent upper gastrointestinal endoscopy revealed signet-ring cell carcinoma in the stomach, and the bilateral breast lesions were diagnosed as metastases of gastric carcinoma. The second case was a 34-year-old female diagnosed with cervical metastasis of signet-ring cell carcinoma who was referred to the breast cancer clinic because of a nodule in the left breast detected by computed tomography. Ultrasonography showed a hypoechoic nodule that was enhanced on gadolinium-enhanced magnetic resonance imaging. Because the pathologic findings for the left breast nodule were quite similar to those of gastric cancer and its cervical metastasis, the breast nodule was diagnosed as a metastasis of gastric carcinoma. When a breast tumor is suspected to have metastasized from a primary tumor in another organ, particularly if signet-ring cells are found, the possibility that gastric cancer is present should be considered.

Lipid-rich carcinoma of the breast that is strongly positive for estrogen receptor: a case report and literature review.

Lipid-rich carcinoma (LRC) of the breast is a rare breast cancer variant that accounts for <1% of all breast malignancies. It has been reported that LRCs are negative for estrogen receptor. Here, we report a case of LRC of the breast that was strongly positive for estrogen receptor and treated with endocrine adjuvant therapy. A 52-year-old postmenopausal female noticed a lump in her right breast by self-examination and presented to our hospital. Physical examination revealed an elastic 30 mm ×20 mm hard mass in the upper medial part of her right breast. The findings obtained using ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging suggested breast cancer. Core needle biopsy resulted in the diagnosis of invasive carcinoma. The patient underwent mastectomy and sentinel lymph node biopsy. Histopathologically, the tumor cells were abundant in foamy cytoplasm. Because the presence of marked cytoplasmic lipid droplets was confirmed by Sudan IV staining and electron microscopic examination of the tumor and the lipid droplets were negative for periodic acid–Schiff staining, the tumor was diagnosed as an LRC. Immunohistochemically, estrogen and progesterone receptors of the tumor were strongly positive, human epidermal growth factor receptor type 2 was negative, and the ratio of Ki-67-positive cells was ~30%. After surgery, the patient underwent combination chemotherapy with anthracycline, cyclophosphamide, and 5-fluorouracil, followed by docetaxel. Thereafter, the pateint was treated with letrozole and has remained well for 24 months with no signs of recurrence.

PATZ1 knockdown enhances malignant phenotype in thyroid epithelial follicular cells and thyroid cancer cells

This study was designed to examine the involvement of PATZ1 in carcinogenesis and dedifferentiation of thyroid cancer. Immunohistochemistry on clinical specimens indicated nuclear PATZ1 expression in all normal thyroid glands and adenomatous goiter, while nuclear PATZ1 expression decreased along with the dedifferentiation of thyroid cancer. Knockdown of nuclear PATZ1 by siRNA in an immortalized normal follicular epithelial cell line (Nthy-ori 3-1) altered cellular morphology and significantly increased cell proliferation, migration, and invasion. In addition, the expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase (MMP) 2, MMP9, and MMP11 was increased by PATZ1 knockdown in Nthy-ori 3-1 cells. When PATZ1 was silenced in differentiated thyroid cancer (DTC) cell lines (TPC-1 and FTC-133), proliferation, cellular motility, and expression of uPA and MMPs were significantly increased. Forced expression of exogenous PATZ1 decreased proliferation, cellular motility, and the expression of uPA and MMPs in ATC cell lines (ACT-1 and FRO). In thyroid cancer cell lines, PATZ1 functioned as a tumor suppressor regardless of p53 status. Moreover, the ratio of nuclear PATZ1 positive tumors was significantly decreased in ATC irrespective of p53 status. Our study demonstrates that PATZ1 knockdown enhances malignant phenotype both in thyroid follicular epithelial cells and thyroid cancer cells, suggesting that PATZ1 functions as a tumor suppressor in thyroid follicular epithelial cells and is involved in the dedifferentiation of thyroid cancer.

Chylous leakage after axillary lymph node dissection in a patient with breast cancer

A 69-year-old woman presented to our hospital with a lump in her left breast. The patient was diagnosed as having stage IIA breast cancer and underwent left mastectomy and axillary lymph node dissection. Axillary lymph nodes at levels I and II were dissected with the axillary vein as the superior border, the latissimus dorsi muscle as the lateral border, and the serratus anterior muscle as the medial border. No unusual events occurred during the operation. Two drains were placed anterior to the major pectoral muscle and the axillary cavity. The histological examination confirmed an invasive ductal carcinoma of 33 mm. Two metastatic lymph nodes were detected. Her postoperative course was uneventful. The patient had a normal diet on the first day after the surgery, and the drainage from the axillary cavity was serous. The drain anterior to the pectoralis major muscle was removed on postoperative day (POD) 3, and the drain in the axillary cavity was removed on POD 11. The patient was discharged on POD 12. On POD 14, the patient visited the outpatient clinic with a slight swelling of axilla. Fifteen milliliters of a milky fluid was aspirated by centesis of the axillary cavity. We took a wait-and-see approach. On POD 21, the patient presented again with swelling of the axilla, and 400 mL of milky fluid was aspirated by centesis (Figure 1). A biochemistry analysis of the drainage fluid revealed 2246 mg/dL of triglycerides. Chylous leakage was identified as the cause of the fluid collection. The patient was admitted to the hospital on POD 22 for conservative treatment. Compression of the axillary cavity by bandage was initiated under a food-deprived condition. The triglyceride concentration had decreased to 545 mg/dL on POD 26. The patient began a low-fat diet on POD 30 and compression of the axillary cavity was removed on POD 31. No accumulation of seroma or chyle in the axilla occurred after removing the compression. Chylous leakage after axillary dissection in breast cancer patients is a very rare complication because the thoracic duct usually has no direct anatomical relation to the axilla. To date, only 31 cases, including our case, have been reported in the literature. Because of its rarity, the appropriate management for chylous leakage of the axilla is controversial. The clinical features of the 31 cases are summarized in Table 1. Twenty-nine (93.5%) cases of chylous leakage occurred in the left axilla. The higher incidence on the left side may result from anatomical reasons: the thoracic duct begins in the abdomen in the left side, crosses the midline to the left side at the level of the aortic arch and continues ascending until it reaches the root of the neck where it joins the venous system. With regard to treatment, 25 (80.6%) patients recovered with conservative treatment and 6 (19.4%) patients received surgery. Conservative treatments such as drainage, diet control, and compression is believed to have been

Abstract 906: PATZ1 promotes migration and invasion of thyroid cancer cells through upregulation of the activity of plasminogen activator and matrix metalloproteinases

Background: PATZ1, a transcription regulator, has been reported to function as oncogene or tumor suppressor in several human malignant neoplasms. The aim of the study was to examine involvement of PATZ1 in carcinogenesis and progression of thyroid cancer. Materials and methods: PATZ1 expression in 165 clinical thyroid specimens obtained from 87 patients were evaluated by IHC. We examined the function of PATZ1 using an immortalized normal thyroid follicular epithelial cell line (Nthy-ori 3-1), and four thyroid cancer cell lines; TPC-1 (papillary cancer), FTC-133 (follicular cancer), FRO and ACT-1 (anaplastic cancer). Knockdown of PATZ1 in Nthy-ori 3-1 and thyroid cancer cell lines was performed with siRNA-PATZ1, and overexpression of PATZ1 in thyroid cancer cell lines was performed with pcDNA3-FLAG-PATZ1. Results: In the IHC analysis of clinical specimens, nuclear PATZ1 expression in anaplastic carcinoma was significantly less frequently than that in normal thyroid tissue or well-differentiated carcinoma (Table 1). Knockdown of PATZ1 in Nthy-ori 3-1 and differentiated thyroid cancer cell lines (TPC-1, FTC-133) induced morphological change of the cells and significant increase of cell proliferation and migration as well as moderate increase of invasion. Furthermore, the expression of u-PA, MMP2 and MMP11 was increased by inhibition of PATZ1 in TPC-1 and FTC-133. On the other hand, overexpression of PATZ1 in anaplastic cancer cell lines (FRO and ACT-1) decreased proliferation and migration of the cells along with the decreased expression of u-PA, MMP2, MMP9 and MMP11. Conclusion: Our study suggests that PATZ1 might play an important role as a tumor suppressor in thyroid follicular epithelial cells and might be involved in progression of thyroid cancer. Citation Format: Asumi Iesato, Teruo Nakamura, Tsuyoshi Uehara, Hiroto Izumi, Ken-ichi Ito. PATZ1 promotes migration and invasion of thyroid cancer cells through upregulation of the activity of plasminogen activator and matrix metalloproteinases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 906. doi:10.1158/1538-7445.AM2017-906

A Case of Adenomyoepithelioma of the Breast Showing Strong Uptake of 18F‐Fluorodeoxyglucose on a Positron Emission Tomography

An adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. This tumor is generally considered as a benign neoplasm, and there are few reports describing the imaging features of this tumor through 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Here, we report a case of an adenomyoepithelioma that showed strong uptake of FDG on PET similar to that observed with a malignant tumor. A 73‐year‐old woman presented to our hospital with a 3.5‐cm, mobile, and elastic hard tumor in the upper area of the left breast. Although the findings of mammography, ultrasonography, and contrast‐enhanced magnetic resonance imaging suggested that the tumor was malignant, it was diagnosed as an adenomyoepithelioma by core needle biopsy. An invasive ductal carcinoma, 0.5‐cm in size, was detected in the medial upper area of the ipsilateral breast during an examination. Although FDG‐PET demonstrated no lymph node or distant metastases from the invasive ductal carcinoma, strong uptake of FDG was detected in the adenomyoepithelioma. Breast conserving surgery and sentinel lymph node biopsy for the invasive ductal carcinoma together with resection of the adenomyoepithelioma was performed. A diagnosis of adenomyoepithelioma was confirmed through histologic examination of the resected specimen. This case indicates that some adenomyoepitheliomas may show a strong uptake of FDG on PET, which resembles a malignant tumor.

rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer

Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient’s entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual compression, the patient required blood transfusion for the massive blood loss. She eventually succumbed to respiratory failure. This case report demonstrates that primary breast cancer lesions with skin involvement have the potential to cause massive hemorrhage after bevacizumab-based treatment.

Abstract P5-08-13: Alteration of sensitivity to chemotherapeutic agents in tamoxifen resistant estrogen receptor positive breast cancer

Background: In the treatment of estrogen receptor (ER) positive recurrent breast cancer, sequential treatment with endocrine or chemotherapy is generally used. However, there is no indicator by which we can select the appropriate chemotherapeutic agent to the endocrine resistant breast cancer in the subsequent treatment. The purpose of this study is to examine whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER positive breast cancer cells. Materials and methods: Three ER positive breast cancer cell lines (T47D, MCF7, BT474) and their tamoxifen (TAM) resistant derivatives (T47D/T, MCF7/T, BT474/T) were established and analyzed for sensitivity to doxorubicin (DOX), 5FU and paclitaxel (PTX). The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. Results: MCF7/T became more sensitive to DOX and 5FU compared with the parental MCF7. In addition, the apoptosis induced by 5FU was significantly increased in MCF7/T compared with the parental MCF7. On the other hand, no difference of sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T compared with their parental cell lines. In MCF7/T and T47D/T, the expressions of dihydropyrimidine dehydrogenase ( DPD) were significantly decreased compared with those in the parental cell lines, while no difference was observed in the expression of thymidine synthase (TS). The expression of thymidine phosphorylase (TP) was decreased in MCF7/T. Conclusion: Our data demonstrate that the sensitivity to 5FU might be altered in a subset of ER positive breast cancer cells, and suggest a possibility that the sensitivity to the chemotherapeutic agents might be modified by the preceding endocrine therapy in ER positive breast cancer cells. We are analyzing drug sensitivity in tumor-bearing mouse model and the data are going to be presented in the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-13.