Enomoto K

Evaluation of follow-up strategies for corticosteroid therapy of idiopathic granulomatous mastitis

PurposeIdiopathic granulomatous mastitis (IGM) is a rare inflammatory pseudotumor. No therapeutic modality has been established because of the rareness of this disease. The aim of this study was to investigate the clinical course of IGM treated with corticosteroid, and to evaluate the optimal methods of observation during corticosteroid therapy of IGM.MethodsThe retrospective study included eight women who met the required histological criteria of IGM. The clinical data of the presentation, histopathology, and management were analyzed by reviewing the medical records.ResultsThe mean age of the patients was 44.8 years (range, 28–75 years) and all patients complained of a breast mass. Seven of them had pain. All of them underwent a core needle biopsy and were diagnosed as having IGM. Five took prednisolone orally and three received prednisolone plus antibiotics; one patient of the latter group underwent a resection due to severe pain. Seven patients healed without surgery and it took from 4 to 10 months to achieve a cure. The period until confirmation of the disappearance of a mass was the shortest by palpation, followed by contrast magnetic resonance imaging and ultrasonography in that order.ConclusionSteroid therapy was effective for the treatment of IGM, which was cured without surgery in seven of eight cases. Ultrasonography was considered an excellent method for evaluating the treatment outcomes.

Primary Hyperparathyroidism with Thyroid Hemiagenesis

Thyroid hemiagenesis is a very rare anomaly. We herein report a case with right thyroid lobe agenesis, which was incidentally found during the assessment of primary hyperparathyroidism. A 42-year-old male presenting with urinary lithiasis was suspected of having primary hyperparathyroidism, and had elevated levels of both serum calcium and intact parathyroid hormone. Both computed tomography and ultrasonography demonstrated the absence of right thyroid lobe and a mass of 1 cm in diameter at the left lower pole of the thyroid. The patient underwent lower left parathyroidectomy, which confirmed the right thyroid hemiagenesis, as well as the absence of both upper and lower right parathyroid glands. The resected left lower parathyroid gland was pathologically diagnosed as adenoma. The postoperative course was favourable and he was discharged on the 2nd day after surgery, without complications.

CYP3A4 expression to predict treatment response to docetaxel for metastasis and recurrence of primary breast cancer

PurposeTumors expressing high levels of CYP3A4 are likely to have a poor treatment response to docetaxel (DOC), which is metabolized by CYP3A4. Tissue samples of recurrent breast cancer are sometimes hard to obtain just before treatment because the tumor is often difficult to access. Using immunohistochemistry, we measured CYP3A4 expression in primary lesions and compared their treatment responses to DOC with those of recurrent breast cancer lesions.MethodsThe subjects of this study were 42 patients who had undergone surgery for breast cancer, and had metastasis or recurrence treated by DOC (60 mg/m2 every 3 weeks). Tumor samples resected at surgery were immunostained for CYP3A4 and its expression levels were compared with the response rate to ongoing DOC treatment.ResultsPatients with CYP3A4-negative tumors (n = 19) showed a significantly higher response rate (63.2%) to DOC treatment than did those with CYP3A4-positive tumors (n = 23) (26.1%). The predictive value, negative predictive value, and diagnostic accuracy of CYP3A4 expression in the prediction response to DOC were 63.2%, 73.9%, and 68.6%, respectively.ConclusionsMeasuring CYP3A4 expression immunohistochemically in the primary breast cancer lesion was useful for predicting the treatment response to DOC of tumors that recurred after a long interval.

Altered intracellular region of MUC1 and disrupted correlation of polarity-related molecules in breast cancer subtypes

MUC1 glycoprotein is overexpressed and its intracellular localization altered during breast carcinoma tumorigenesis. The present study aimed to clarify the relationship of cytoplasmic localization of MUC1 with the breast cancer subtype and the correlation of 10 molecules associated with cell polarity in breast cancer subtypes. We immunostained 131 formalin‐fixed and paraffin‐embedded breast cancer specimens with an anti‐MUC1 antibody (MUC1/CORE). For 48 of the 131 tumor specimens, laser‐assisted microdissection and real‐time quantitative RT‐PCR were performed to analyze mRNA levels of MUC1 and 10 molecules, β‐catenin, E‐cadherin, claudin 3, claudin 4, claudin 7, RhoA, cdc42, Rac1, Par3 and Par6. Localization of MUC1 protein varied among breast cancer subtypes, that is, both the apical domain and cytoplasm in luminal A‐like tumors (P < 0.01) and both the cytoplasm and cell membrane in luminal B‐like (growth factor receptor 2 [HER2]+) tumors (P < 0.05), and no expression was found in triple negative tumors (P < 0.001). Estrogen receptor (ER)+ breast cancers showed higher MUC1 mRNA levels than ER− breast cancers (P < 0.01). The incidence of mutual correlations of expression levels between two of the 10 molecules (55 combinations) was 54.5% in normal breast tissue and 38.2% in luminal A‐like specimens, 16.4% in luminal B‐like (HER2+), 3.6% in HER2 and 18.2% in triple negative specimens. In conclusion, each breast cancer subtype has characteristic cytoplasmic localization patterns of MUC1 and different degrees of disrupted correlation of the expression levels between the 10 examined molecules in comparison with normal breast tissue.

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma

Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.

Menstruation recovery after chemotherapy and luteinizing hormone-releasing hormone agonist plus tamoxifen therapy for premenopausal patients with breast cancer.

PurposeLittle is known about the period required for menstruation recovery after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen therapy following chemotherapy. In this study we investigated the period required for menstruation recovery after the therapy.MethodsThe subjects comprised 105 premenopausal breast cancer patients who had undergone surgery. All patients were administered an LH-RH agonist for 24 months and tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the status of menstruation recovery was examined.ResultsMenstruation resumed in 16 cases (15.2%) after the last LH-RH agonist treatment session. The mean period from the last LH-RH agonist treatment to the recovery of menstruation was 6.9 months. The rate of menstruation recovery was 35.5% in patients aged 40 years or younger and 8.0% in those aged 41 years or older, and it was significantly higher in those aged 40 years or younger. The period until menstruation recovery tended to be longer in older patients at the end of treatment.ConclusionThis study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.

Ultrasonographic findings: an unusual case of secondary leiomyosarcoma after radiotherapy for breast cancer.

A 66-year-old female was admitted to our department for palpable swelling of the left breast skin region (Fig. 1). The skin tumors were 1.6 and 1.5 cm in diameter, respectively, with a 5-month history. Eighteen years previously, the patient had been treated with modified radical mastectomy and dissection of axillary lymph nodes for left-sided breast cancer. Histological evaluation revealed an invasive ductal carcinoma 3.2 cm in size. A lymph node excised from her left axilla at the time did not show any evidence of metastasis. The clinicopathological stage, according to the UICC-pTNM classification, was Stage IIA. Postoperatively, she was given a course of external beam radiotherapy to the left breast and axilla (35 Gy in 10 fractions). A boost of 10 Gy in four fractions was given to the scar. Adjuvant endocrine therapy with tamoxifen, 20 mg daily, was administered for 5 years post operation. Following this, she had remained free of cancer recurrence. Clinically, there was a high suspicion of post-irradiation tumors. The tumors were found in the integument about 4 cm away from the area wounded by the breast cancer treatment performed in the past. The surface of the tumors was red and rugged. The border of the tumors was clear. There was no adhesion between the tumors and the chest wall. The blood chemistry results, including tumor markers, were normal. Contrast-enhanced computed tomography (CT) showed the tumors as highly enhanced with irregular margins (Fig. 2). The result of aspiration biopsy cytology (ABC) was Class IIIb. The tumors were seen on ultrasonography (APILIO, Toshiba, Tokyo, Japan) as hypoechoic masses, 16 9 17 mm and 15 9 17 mm, with ill-defined borders, irregular margins, and internal heterogeneity (Fig. 3). There was a difference in internal heterogeneity between the left tumor and the right tumor. The internal heterogeneity of the left tumor was higher than that of the right tumor. Power Doppler US (Fig. 4a, b) showed rich blood flow in the tumors. The blood flow in both tumors showed a pulsatile flow. No metastases were seen in the brain, lungs, liver, bones, infraclavicular lymph nodes, and axillary lymph nodes on CT and bone scintigram. The patient was submitted to wide excision plus resection of a portion of the serratus anterior muscle close K. Sakurai (&) K. Enomoto Division of Breast and Endocrine Surgery, Department of Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan e-mail: ksakurai@med.nihon-u.ac.jp

Ultrasonographic findings for breast carcinoma with osteoclast-like giant cells

A 72-year-old woman visited our department with an enlarged palpable mass which was 2 cm in diameter, painless, and well-demarcated. She had noticed the mass four months earlier. The family history and her past medical history were unremarkable. On arrival, a movable tumor of 2 cm in diameter was palpated in the upper-outerquadrant of the right breast. The ipsilateral axillary lymph nodes were not palpable. The blood chemistry results, including tumor markers, were normal. Mammography revealed a mass with ill-defined borders and higher central density in the right breast (Fig. 1). The tumor was seen by breast ultrasonography (Apilio, Toshiba, Tokyo, Japan) as a low echoic mass, 28 mm 9 24 mm, with ill-defined borders, irregular margins, and internal heterogeneity (Fig. 2). Doppler US (Fig. 3) and power Doppler US (Fig. 4) showed a rich blood flow in the tumor. Contrastenhanced magnetic resonance imaging (MRI) showed the tumor to be highly enhanced with irregular margins (Fig. 5). The time-intensity curve showed an early peak and plateau pattern, suggesting malignancy. Pathological findings from a core needle biopsy revealed an infiltrating ductal carcinoma of the breast. Estrogen receptor (ER) and progesterone receptor (PgR) tests were positive, and the HER-2 score was 0. No metastases were seen in the brain, lungs, liver, bones, infraclavicular lymph nodes, or axillary lymph nodes by computed tomography (CT) and bone scintigram. With a diagnosis of right breast cancer (T2N0M0 = Stage IIA), a right modified radical mastectomy and biopsy of sentinel lymph nodes were performed. According to the intra-operative rapid pathological diagnosis, the sentinel lymph nodes were negative for metastasis. The final pathological diagnosis was an invasive ductal carcinoma (papillotubular carcinoma) with OGCs (Fig. 6). Immunohistochemical analysis demonstrated that the OGCs were CD68 and vimentin positive, but negative for cytokeratin, S-100, and a-smooth muscle actin. The clinicopathological stage, according to the UICC-pTNM classification, was Stage IIA.

The Merits and Demerits of Reorganization in the Department of Surgery, Nihon University School of Medicine-From the Perspective of the Division of Breast and Endocrine Surgery-

目的：日本大学医学部付属板橋病院外科系診療科の臓器別再編の効用について乳腺内分泌外科の立場から検討する．方法：再編前後の 4 年間について乳腺内分泌疾患のみを対象とし，手術件数，乳房温存率，1 日平均外来患者数，1 日平均入院患者数，初診察患者数，紹介率，外来年間延べ患者数，入院年間延べ患者数，外来 1 人 1 日平均収入，入院 1 人 1 日平均収入，総医療発生額を検討した．結果：手術件数，乳房温存率，1 日平均外来患者数，初診察患者数，外来年間延べ患者数，外来 1 人 1 日平均収入，総医療発生額は再編後の方が有意に増加していた．結語：外科系診療科を臓器別に再編し，患者や周辺医療機関に扱う領域がわかりやすくなったことで，初診患者数が増加し，手術件数や収入が上昇した．診療科の臓器別再編は意義のあることと考えられた．

Atypical medullary carcinoma of the breast.

A 57-year-old woman was seen in our department for pain in the left breast, which had been noticed two months earlier. Her family history and past medical history were unremarkable. On arrival, a movable tumor 2 cm in diameter was palpated in the upper-outer-quadrant of the left breast. The ipsilateral axillary lymph nodes were not palpable. Blood chemistry results, including tumor markers, were normal. Mammography revealed a mass that had ill-defined borders and a higher central density with some spiculations in the left breast. The diagnosis was category 5 (Fig. 1). The tumor was seen by breast ultrasonography (Aplio, Toshiba, Tokyo, Japan) as a low echoic mass, 28 9 27 mm, with ill-defined borders, irregular margins, and internal heterogeneity. The anterior border was disrupted by tumor invasion (Fig. 2). Power Doppler US showed rich blood flow in the tumor (Fig. 3). Contrast-enhanced magnetic resonance imaging (MRI) showed the tumor as highly enhanced with irregular margins (Fig. 4). The time–intensity curve was an early peak and plateau pattern, suggesting malignancy. Pathological findings from a core needle biopsy revealed an infiltrating ductal carcinoma of the breast. Estrogen receptor (ER) and progesterone receptor (PgR) were positive, and the HER-2 score was 2?. No metastases were seen in the brain, lungs, liver, bones, abdominal cavity lymph nodes, infraclavicular lymph nodes, and axillary lymph nodes by computed tomography (CT) and bone scintigram. With a diagnosis of left breast cancer (T2N0M0 = Stage IIA), left quadrantectomy and biopsy of sentinel lymph nodes were performed. According to the intra-operative rapid pathological diagnosis, the sentinel lymph nodes were negative for metastasis. However, an intraductal carcinoma was noted at the resection margin on the papillary side of the resected breast tissue. Therefore, a pectoral muscle-sparing mastectomy was performed. The final pathological diagnosis was atypical medullary carcinoma (Fig. 5).