HER2-positive breast cancer in a germline BRCA1 gene large deletion carrier.

A majority of breast cancer (BC) molecular subtype in BRCA1 variants carriers is triple-negative type. In contrast, human epidermal growth factor 2 (HER2)-positive BC among carriers of BRCA1 variants is rarely reported. A 42-year-old woman who previously received adjuvant endocrine therapy against left BC developed a left BC relapse and a right new primary BC. Her mother had BC and ovary cancer, and her cousin had BC. Genetic testing revealed a pathogenic large deletion of exons 1-8 in BRCA1. She was diagnosed with hereditary breast and ovary cancer and underwent bilateral mastectomy. The molecular subtypes of her right and left primary BC were HER2-enriched type and luminal-HER2 type, respectively. After completion of adjuvant therapy for right BC, risk-reducing salpingo-oophorectomy (RRSO) is planned. The present case makes us consider the frequency of BRCA1 large rearrangements in Japanese, the association between HER2 amplification and BRCA1 variants, and the optimal timing of RRSO in patients receiving adjuvant therapy for BC.

Mucosa-associated lymphoid tissue (MALT) lymphoma developing in ectopic mediastinal thyroid tissue: a case report.

BACKGROUND: Normally located in the neck, ectopic mediastinal thyroid tissue consists of very rare ectopic thyroid tissue that does not connect to the thyroid gland. A patient with mucosa-associated lymphoid tissue (MALT) lymphoma that has developed in mediastinal thyroid tissue, to our best knowledge, has not been previously reported. CASE PRESENTATION: A 67-year-old woman presented with a superior mediastinal mass that was revealed by chest computed tomography (CT), an optional examination she hoped, during a medical checkup. Contrast-enhanced CT scan performed in our hospital for close examination confirmed the presence of a 2 × 1.3 cm poorly enhanced mass anterior to the trachea during the arterial phase. Magnetic resonance imaging depicted low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. I-131 meta-iodobenzylguanidine did not accumulate in the mass. Serum levels of interleukin-2 receptor, catecholamine, and anti-acetylcholine receptor antibody were within the normal range. The mass was resected through a transverse neck incision for the diagnosis and treatment. The histopathological diagnosis of the specimen was ectopic mediastinal thyroid tissue associated with MALT lymphoma and chronic thyroiditis. Immunoglobulin heavy chain class switch recombination was identified. Fine-needle aspiration biopsy of the cervical thyroid showed chronic thyroiditis but not lymphoma. The patient's postoperative thyroid function was normal. To date, the patient's recovery has been uneventful, and she is being monitored without further treatment. CONCLUSION: We treated the patient with MALT lymphoma that developed in ectopic mediastinal thyroid tissue. This novel case illustrates a new differential diagnosis associated with ectopic mediastinal thyroid tissue.

Thyroidectomy in a patient with thyroid storm: report of a case.

Thyroid storm is a life-threatening condition that is generally considered to be a contradiction to surgical intervention. We herein describe the case of a 37-year-old patient with a history of Graves' disease who was transferred to Tottori University Hospital with thyroid storm. She had been followed by her family doctor since 2006, but she had stopped taking her medication of her own volition in 2010. About ten days prior to her admission at our hospital, she consulted her family doctor with complaints of dyspnea, palpitations and general fatigue. Subsequent thyroid function tests showed TSH < 0.01 µU/ml, FT3 25.0 pg/ml and FT4 8.0 ng/dl. She also had acute heart failure, atrial fibrillation and hepatic failure. A diagnosis of thyroid storm was made and she was transferred to our hospital. She received steroids, beta blockade, potassium iodide, and plasma exchange, but her hepatic failure did not resolve and her clinical condition deteriorated. The decision was made to proceed with thyroidectomy. Postoperatively, her hepatic function normalized. Thus, thyroidectomy is a potential therapeutic choice for cases of thyroid storm refractory to medical management.

Elective treatment of middle colic artery aneurysm.

Middle colic artery aneurysms are rare and most have been reported with rupture or symptom. We report the successful elective treatment of a middle colic artery aneurysm without symptom, which is very rare. It failed to perform transcatheter arterial embolization for anatomical reasons, and, thus, the patient, a 77-year-old man, underwent surgical resection in spite of a history of laparotomy. Although a common cause of middle colic artery aneurysms is segmental arterial mediolysis, the present pathological findings indicated that fragmented or degenerated elastic fibers may also play an important role like aortic aneurysms.

Effect of chemotherapy for luminal a breast cancer.

BACKGROUND: The addition of chemotherapy to endocrine therapy for luminal A breast cancer generally provides little benefit. However, the least benefit of chemotherapy in all patients with luminal A breast cancer is controversial. METHODS: This was a retrospective study of 140 patients with luminal A breast cancer who underwent surgery at Tottori University Hospital between 2001 and 2010. Luminal A breast cancer was defined as positive for estrogen receptors and/or progesterone receptors and negative for human epidermal growth factor 2. Postoperative endocrine therapy was given to all patients. The prognostic values of age, tumor size, presence of lymphovascular invasion and lymph node status were evaluated. In addition, the prognostic value of chemotherapy for patients with identified risk factors affecting relapse-free survival and overall survival was evaluated. RESULTS: Tumor size greater than 2 cm and positive lymph node status were factors significantly affecting relapse-free survival. There were no factors significantly affecting overall survival. There was no significant difference in the relapse-free survival of patients with tumor size greater than 2 cm and/or positive lymph node status who either received chemotherapy or not. However, the relapse event was earlier in patients with tumor size greater than 2 cm and positive lymph node status who did not receive chemotherapy than in those who received chemotherapy. CONCLUSION: Chemotherapy could provide little benefit to patients with luminal A breast cancer. However, chemotherapy may bring them longer relapse-free periods.

Pheochromocytoma multisystem crisis successfully treated by emergency surgery: report of a case.

Pheochromocytomas are rare neuroendocrine tumors that produce symptoms through the excess release of catecholamines. The treatment of choice is a complete surgical removal after pretreatment with an α-blocker, to prevent dangerous hemodynamic fluctuations. Newell and colleagues defined the rare, fatal condition of catecholamine crisis, which includes multiple organ failure (MOF), severe blood pressure variability, high fever, and encephalopathy, as pheochromocytoma multisystem crisis (PMC). The indications for emergency surgery in this unstable state still remain controversial. This report presents the case of a 52-year-old female patient with PMC who successfully underwent a surgical resection. This case showed that early tumor removal may be the only means of halting the progression of this disease.

ACTH-Producing Breast Cancer: A Patient Report.

Ectopic ACTH secretion in the setting of breast cancer is extremely rare but when present affects both the tumor's behavior and the incidence of complications. The patient, a 58-year-old woman, first presented with a mass in her left breast as well as multiple osseous metastases and a right femur fracture. Laboratory data revealed a hypokalemic alkalosis. Her plasma ACTH level was elevated. She was diagnosed with breast cancer with ectopic ACTH secretion, and underwent a left mastectomy and axillary lymph node dissection. Histological examination demonstrated a poorly differentiated neuroendocrine carcinoma with ectopic ACTH secretion. Although the signs and symptoms of ectopic ACTH secretion from a breast cancer are frequently subtle, the recognition of ectopic ACTH secretion from breast cancer is important for patient management.

[A case of aggressive primary squamous cell carcinoma of the breast refractory to preoperative neoadjuvant chemotherapy].

A 42-year-old woman came to our hospital complaining of an enlarging tumor in her right breast. A core needle biopsy of the involved area demonstrated primary squamous cell carcinoma (SCC) of the breast. Preoperative neoadjuvant chemotherapies included 5-fluorouracil: 5-FU+epirubicin: EPI+cyclophosphamide: CPA (FEC), paclitaxel (PTX), vinorelbine (VNR) and 5-FU+nedaplatin (254-S) given in the order listed, but the mass continued to enlarge. Therefore, surgical resection was performed. Local recurrence and lung metastasis occurred after surgery. Although postoperative adjuvant chemotherapy consisting of carboplatin (CBDCA) +etoposide (VP-16) was administered, the patient died three months after surgery. SCC of the breast is generally treated according to clinical stage using protocol for common types of breast cancer. However, effective regimens have not been established for SCC, because it tends to be treatment-refractory. Therefore, in patients with SCC, it is important to consider surgery at an earlier stage than would be considered for a common breast cancer requiring preoperative neoadjuvant chemotherapy.

Large-cell carcinoma of the lung with a remarkable preoperative elevation of serum carcinoembryonic antigen level.

Carcinoembryonic antigen, a serum tumor marker, is useful for diagnosing cancer and for following the response to therapy in cancer cases. Serum carcinoembryonic antigen levels are also important as a predictive tool in evaluating prognosis. A 56-year-old man presented with an abnormal shadow on a chest X-ray. His preoperative serum carcinoembryonic antigen was at an elevated level of 1274.0 ng/ml. Chest computed tomography revealed a tumor in the posterior segment of the right lung and a swollen right interlobar lymph node. Right lung pneumonectomy and node dissection were performed. A histological diagnosis determined that the tumor was a large-cell carcinoma at clinical stage IIA. Immunohistochemical analysis detected the production of carcinoembryonic antigen by the tumor cells. Following surgery, the patient's carcinoembryonic antigen levels were maintained within the normal range. This is a rare case of lung cancer with no evidence of recurrence and metastasis for 8 years despite markedly elevated preoperative carcinoembryonic antigen levels.

Needle track dissemination of follicular thyroid carcinoma following fine-needle aspiration biopsy: report of a case.

Few reports have been concerned with the risk of needle track dissemination of tumor cells following fine-needle aspiration biopsy, especially for follicular thyroid nodules. A 61-year-old woman who underwent fine-needle aspiration biopsy and surgery 5 years previously for follicular thyroid adenoma presented with nodules that had developed in the sternocleidomastoid and omohyoid muscles of the anterior neck. These nodules were located along a line from the skin to the thyroid that coincided with the needle track of the previous biopsy. Following surgical resection, histological diagnosis determined the nodules to be follicular carcinoma. The clinical course and linear arrangement of the lesions were highly suggestive of needle track dissemination of tumor cells following fine-needle aspiration biopsy. Although fine-needle aspiration biopsy is a useful tool for the diagnosis of thyroid nodules, it is important to consider the risk of tumor cell dissemination.

Identification of secernin 1 as a novel immunotherapy target for gastric cancer using the expression profiles of cDNA microarray.

Despite the discovery of multiple TAAs, only a limited number is available for clinical application, particularly against epithelial malignancies. In this study we searched for novel TAAs using expression profiles of gastric cancer examined with cDNA microarray, and identified the SCRN1 gene as a candidate. SCRN1 was confirmed to be expressed in five out of seven gastric cancers with semiquantitative RT-PCR. With Northern blot analysis, it was detected abundantly in the testis and ovary, but it was barely detectable in 14 other normal human adult organs. Colony formation assay revealed that its augmented expression is associated with promoted cell growth. As these expression profiles and functional features of SCRN1 appeared to be compatible with the characteristics of the hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic epitope peptides restricted to HLA-A*0201. We synthesized the candidate peptides derived from SCRN1, and tried to induce CTLs with each peptide. The CTL clones were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed not only the peptide-pulsed targets but also the tumor cells expressing both SCRN1 and HLA-A*0201 endogenously. These results strongly suggest that SCRN1-196 is an epitope peptide restricted to HLA-A*0201. Furthermore, we synthesized an anchor-modified peptide SCRN1-9 V (KMDAEHPEV), in which leucine at position 9 was substituted for valine to increase the binding affinity to the HLA-A*0201 molecules. The CTL clones induced by SCRN1-9 V also recognized tumor cells expressing its natural SCRN1 protein endogenously. These results strongly suggest that SCRN1 is a novel TAA and these peptides, both native and modified, may be applicable for cancer vaccines to treat gastric cancer.

Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas.

We previously performed gene expression profile analyses of 20 intestinal-type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non-cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer-testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11-specific CTL. As a result, we successfully established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor-modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers.

Ring finger protein 43 as a new target for cancer immunotherapy.

We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.