[Pulmonary Mucoepidermoid Carcinoma with Hilar Lymph Node Metastasis Complicated by Myelodysplastic Syndrome].

A 65-year-old woman was found to have a mass shadow on chest computed tomography. The patient had been diagnosed as having myelodysplastic syndrome 3 years before admission. She was transferred to our hospital for further examination of the mass in the lower lobe of left lung. The mass was positron emission tomography-positive (SUVmax of 8.6)suggesting a malignant neoplasm. Serum concentrations of carcinoembryonic antigen was elevated to 8.7 ng/ml. Preoperative laboratory studies showed anemia (hemoglobin 6.9 g/dl). Transfusion of red blood cells was performed prior to surgery. Under the video-assited thoracoscopic surgery, left lower lobectomy and lymph node dissection were perfomed. The histopathological diagnosis was mucoepidermoid carcinoma, and the hilar lymph node metastasis positive. There were no postoperative complications, such as infection or bleeding. Chemotherapy with tegafur/uracil was performed after the operation. The patient is currently alive without any recurrence 2 years after the operation.

Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma.

HER-3 expression has been reported to act as an important oncoprotein in head and neck squamous cell carcinoma. This protein is known to control tumor proliferation and acquisition of resistance by tumor cells towards EGFR inhibitors, therefore, development of a HER-3-targeted therapy is desirable. In this study, we found that HER-3 expression on tumor cells was increased after EGFR inhibition. To establish a novel therapeutic approach for HER-3-positive head and neck carcinoma, we identified a HER-3 helper epitope that could elicit effective helper T cell responses to the naturally processed HER-3-derived epitope presented in a HER-3 expressing tumors. This epitope induced potent cytolytic activity of CD4 T cells against such tumor cells. Moreover, pan HER-family tyrosine kinase inhibitor augmented the responses of HER-3-reactive CD4 T cells via upregulation of HLA-DR protein on the surface of tumor cells. Our results supports the validity of CD4 T cell-dependent HER-3-targeted therapy combined with a broad inhibitor of HER-family.

Leiomyosarcoma arising in irradiated region after breast-conserving surgery: a case report.

BACKGROUND: Radiation therapy (RT) is considered a risk factor for the development of sarcoma in patients with breast cancer. However, there are few reports regarding post-irradiation sarcoma (PIS). CASE PRESENTATION: The patient was a 59-year-old woman who presented with a chief complaint of induration in the lower outer quadrant of the left breast. She underwent breast-conserving surgery (BCS) for breast cancer located in the left upper inner region and received endocrine therapy following RT (50 Gy/25 fractions/5 weeks) for breast conservation 6 years previously. Core needle biopsy revealed leiomyosarcoma. There was no distant metastasis. Repeat BCS including part of the pectoralis major muscle was performed. Chest wall resection was not performed because of the lack of invasion. Based on the morphological and immunohistochemical features, a diagnosis of leiomyosarcoma was made. All of the resection margins in the specimen were tumor-free. She has been disease-free for over 20 months. CONCLUSIONS: Post-irradiation leiomyosarcoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised.

c-Met is a novel tumor associated antigen for T-cell based immunotherapy against NK/T cell lymphoma.

Background: The expression of c-Met and its ligand HGF plays a critical role in cell proliferation and is involved in numerous malignancies. Because c-Met expression and its role in NK/T-cell lymphoma remain unclear, we studied the expression and function of c-Met in NK/T-cell lymphoma cells. In addition, we investigated the possibility that c-Met could function as a tumor-associated antigen for helper T lymphocytes (HTLs). Methods: We evaluated whether HGF and c-Met were expressed in NK/T-cell lymphoma and the capacity of predicted c-Met HTL epitopes to induce antitumor responses in vitro. In addition, c-Met inhibitor was evaluated for the ability to inhibit TGF-ß production in tumor and subsequently increase HTL recognition. Results: c-Met and HGF were expressed in NK/T-cell lymphoma cell lines, nasal NK/T-cell lymphoma specimens and patient serum samples. Moreover, HGF was shown to promote NK/T cell lymphoma (NKTCL) proliferation in an autocrine manner. Furthermore, we have identified three novel c-Met HTL epitopes that were restricted by several HLA-DR molecules. Notably, peptide-induced HTL lines directly recognized and killed c-Met expressing NK/T-cell lymphomas and various epithelial solid tumors. The c-Met specific HTLs could also recognize dendritic cells (DCs) pulsed with c-Met expressing tumor cell lysates. In addition, we observed that c-Met inhibition augmented HTL recognition by decreasing TGF-ß production by tumor cells. Lastly, autophagy partly regulated the HTL responses against tumors. Conclusions: We identified novel c-Met HTL epitopes that can elicit effective antitumor responses against tumors expressing c-Met. Our results provide the rationale of combining c-Met targeting therapy and immunotherapy for NKTCLs and epithelial tumors.

Photodynamic diagnosis of pleural malignant lesions with a combination of 5-aminolevulinic acid and intrinsic fluorescence observation systems.

BACKGROUND: We have developed a new diagnostic method using the photosensitizer 5-aminolevulinic acid (5ALA) for diagnosing intrathoracic malignant lesions. When ingested exogenously, 5ALA is metabolized to a heme precursor, protoporphyrin IX, which stays in malignant cells and emits red to pink luminescence of about 630 nm. METHODS: We enrolled 40 patients who underwent respiratory surgery and consented to participate in this study. Twenty-eight patients had primary lung cancer, 8 metastatic lung tumors, 2 malignant pleural tumors, and 2 benign tumors. Localization of malignant lesions was attempted by observing such lesions with an autofluorescence imaging system and by comparing the color tone of the autofluorescence between malignant lesions and normal tissues after oral administration of 5ALA. Malignant lesions on the pleural surface emitted pink autofluorescence in contrast to the green autofluorescence of the surrounding normal tissues. RESULTS: When 28 patients with primary lung cancer were examined according to the degree of pleural infiltration (pl), red fluorescence was confirmed in 10 of 10 patients (100%) with p11-p13 and 5 of 18 patients (27.7%) with p10. The latter 5 patients had been diagnosed with PL1 preoperatively or intraoperatively. CONCLUSION: This system achieved accurate localization of malignant lesions, suggesting that it may also be applicable to photodynamic therapy.

Photodynamic diagnoses of malignant pleural diseases using the autofluorescence imaging system.

BACKGROUND: We conducted a study on photodynamic diagnosis (PDD) using autofluorescence in video-assisted thoracic surgery for minute intrathoracic small dissemination or early malignant pleural mesothelioma. METHODS: Autofluorescence is the spontaneous emission of light that occurs when mitochondria, lysosomes, and other intracellular organelles absorb light. In normal tissues, green autofluorescence of approximately 520 nm is observed in response to 400-450 nm blue excitation rays. However, in cancer lesions, green autofluorescence is reduced due to thickening of the mucosal epithelium, a decrease in autofluorescent substances, etc., and the color spectrum thus shifts to red-violet. This phenomenon is the basis of PDD. RESULTS: The color spectrum shift was observed in all tumors located on the pleural surface but not in cases with pleural fibrous disease. Among patients with primary lung cancer, those with pleural infiltration (pl) scores of 1 or greater showed color spectrum shifts due to reduced autofluorescence. CONCLUSION: Localization of pleural lesions by autofluorescence imaging was found to be useful. In primary lung cancer cases, differentiation between pl0 and pl1 lesions appears to be useful for determining therapeutic strategies including surgical procedures.

Spindle cell carcinoma of the breast as complex cystic lesion: a case report.

Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammography showed a category four mass with a diameter of 2.5 cm. Ultrasonography (US) revealed a complex cystic lesion, and fine-needle aspiration (FNA) cytology demonstrated bloody fluid and malignant cells. Partial breast resection and sentinel lymph node biopsy were performed. Immunohistology revealed spindle cells with positive results for cytokeratin (AE1/AE3) and vimentin, partially positive results for s-100, and negative results for desmin and α-actin. The pathological stage was IIA, and biochemical characterization showed that the tumor was triple negative. Six courses of FEC-100 chemotherapy (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) were administered. Radiotherapy was performed. This case is discussed with reference to the literature.

Induction of tumor-reactive T helper responses by a posttranslational modified epitope from tumor protein p53.

Posttranslational modifications regulate the function and stability of proteins, and the immune system is able to recognize some of these modifications. Therefore, the presence of posttranslational modifications increases the diversity of potential immune responses to a determinant antigen. The stimulation of tumor-specific CD4(+) helper T lymphocytes (HTLs) is considered important for the production of anti-tumor antibodies by B cells and for the generation and persistence of CD8(+) cytotoxic T lymphocytes, and in some instances, HTLs can directly reduce tumor cell growth. Identification of MHC class II-restricted peptide epitopes from tumor-associated antigens including those generated from posttranslational protein modifications should enable the improvement of peptide-based cancer immunotherapy. We describe here an MHC class II binding peptide from the tumor protein p53, which possesses an acetylated lysine at position 120 (p53110-124/AcK120) that is effective in eliciting CD4(+) T cell responses specific for the acetylated peptide. Most importantly, the acetylated peptide-reactive CD4 HTLs recognized the corresponding naturally processed posttranslational modified epitope presented by either dendritic cells loaded with tumor cell lysates or directly on tumors expressing p53 and the restricting MHC class II molecules. Treatment of tumor cells with a histone deacetylase inhibitor augmented their recognition by the p53110-124/AcK120-reactive CD4(+) T cells. These findings prove that the epitope p53110-124/AcK120 is immunogenic for anti-tumor responses and is likely to be useful for cancer immunotherapy.

Histological grade as an alternative to the Ki67 labeling index is only available for luminal-type breast cancers.

BACKGROUND: The 2011 St. Gallen Consensus Statement advocated using histological grade (HG) as a proliferation marker of breast cancer (BC) if reliable Ki67 labeling index (Ki67-LI) assessment is not available. However, it has been difficult to evaluate tumor aggressiveness in case of HG2. METHODS: A total of 259 cases of BC were assessed for HG, Ki67-LI and other clinicopathological features. The cut point for Ki67-LI was interpreted as low and high using a 14% threshold. RESULTS: The average age at diagnosis was 58.2 years (range 28-86); 64.9% of the patients were postmenopausal. Of the 259 cases, 151 were stage I, 78 were stage II, 29 were stage III, and 1 was stage IV. The subtypes based on immunohistochemical staining were 60 cases of luminal A (LA) type (23.2%), 37 cases of luminal B (LB) (HER2-) type (14.3%), 91 cases of LB (HER2+) type (35.1%), 40 cases of human epidermal growth factor receptor 2 (HER2) type (15.4%) and 31 cases of triple negative (TN) type (12%). HG was 1 (89 cases, 34.4 %), 2 (117 cases, 45.2%) and 3 (53 cases, 20.5%). High Ki67-LI cases were observed in HG1 (37.1%), HG2 (56.4%) and HG3 (96.2%). Especially in cases of HG2, high Ki67-LI cases were observed in 0 % of LA type, 100% of LB (HER2-) type, 71.2% of LB (HER2+) type, 68.8% of HER2 type and 40.0% of TN type. The average Ki67-LI was 6.0 ± 3.8 (LA type), 31.4 ± 15.7 [LB (HER2-) type], 20.2 ± 14.8 [LB (HER2+) type], 32.7 ± 21.9 (HER2 type) and 55.7 ± 32.2 (TN type). All LA-type cases and 66.7% of LB (HER2+)-type cases were low Ki67-LI. CONCLUSIONS: Our study demonstrates that all LA-type cases and most HG1 of LB (HER2+)-type cases are low proliferative. However, HG was not informative enough for estimating tumor proliferation in cases of LB (HER2-), HER2 and TN types. It is necessary to add other proliferation tools such as the gene expression profiling tool and Ki67-LI except in LA and HG1 of LB (HER2+)-type cases.

Esophageal schwannoma: a case report.

Most tumorous lesions of the esophagus are esophageal cancers. Benign primary tumors of the esophagus are uncommon, and account for approximately 2% of all esophageal tumors. More than 80% of benign esophageal tumors are leiomyomas, with schwannomas being rare. A 55-year-old woman visited our internal medicine department with complaints of palpitations and discomfort during swallowing. A chest computed tomography scan showed a lobulated tumor (75 × 57 × 80 mm) in the upper to middle mediastinum, with homogenous inner opacity, compressing the esophagus. Upper gastrointestinal endoscopy revealed a smooth-surfaced elevated lesion covered with normal mucosa, and a schwannoma was diagnosed based on the biopsy result. The tumor was large. It was thus considered to be difficult to repair the esophagus by direct anastomosis after tumor resection. Therefore, subtotal esophagectomy and esophagogastrostomy in the right thorax were performed. Histopathological examination revealed spindle-shaped cells in a fasciculated and disarrayed architecture and nuclei in a palisading pattern. Immunohistochemical studies revealed S100 protein positivity and the absence of staining for α smooth muscle actin (αSMA), CD34 and CD117, thereby establishing the diagnosis of benign schwannoma. Her postoperative course was uneventful and there has been no evidence of recurrence to date.

Combined large cell neuroendocrine carcinoma with giant cell carcinoma of the lungs: a case report.

Combined large cell neuroendocrine carcinoma of the lungs (combined LCNEC) with giant cell carcinoma is extremely rare. A 65-year-old man was found to have an abnormal shadow in his left lung field. Computed tomography revealed a solid, round mass measuring 2.8 × 2.2 cm that was located in the left S9. The patient underwent left lower lobectomy and mediastinal lymph node dissection. Histopathological examination revealed an LCNEC, combined with giant cell carcinoma. The patient received by S-1 (TS-1, an oral fluoropyrimidine) chemotherapy, and he has been disease-free for over 8 months. Combined LCNEC with giant cell carcinoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised.

[Intraoperative thracoscopic needle biopsy for the diagnosis of indeterminate pulmonary tumor].

To define the usefulness of intraoperative thracoscopic needle biopsy( ITNB), we compared the background and operative outcomes of the patients underwent ITNB with those of the patients underwent partial lung resection(PLR)using auto-suture devices. Between 2002 and 2009, 78 patients were diagnosed as lung carcinoma by intraoperative pathological examination (IPE) and subsequently performed curative surgery. In these 78 patients, 31 underwent ITNB (NB group)first and 47 underwent PLR (PR group) first. The tumor size, distance between tumor and pleura, number of required auto-suture devices and duration time of surgery in NB group were 34.5±15.6 mm, 9.2±8.6 mm, 4.2±1.5 and 276±47 minutes, respectively. Those in PR group were 27.8±14.2 mm, 7.1±6.8 mm, 5.5±2.0 and 286±61 min utes, respectively. The number of required auto-suture devices in NB group was significantly fewer than that in PR group (p<0.01).The accuracy of IPE was 93.5% and local recurrences weren't observed in NB group. ITNB prior to PLR for the patients with indeterminate lung tumor economizes the auto-suture devices and time required for PLR, so this method might contribute to save the operative cost and duration.

[Pulmonary squamous papilloma].

We report a rare case of pulmonary squamous papilloma. A 42-year-old woman was referred to our hospital complaining of dry cough. A chest computed tomography (CT) showed a mass shadow in the lower lobe of left lung. Serum concentrations of carcinoembryonic antigen (CEA) and squamous cell carcinoma-related antigen (SCC) were elevated to 13.0 ng/ml and 11.8 ng/ml, respectively. The mass was positron emission tomography( PET)-positive, with a maximum standard uptake value( SUVmax) of 11.55, suggesting a malignant neoplasm. Under the guidance of video-assisted thoracoscopy, left basal segmentectomy was performed. Intra-operative diagnosis was a squamous papilloma and no malignancy. Her postoperative course was uneventful. She is currently alive without any sign of recurrence.

A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope.

Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1-transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH(2)-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+ T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.

Surgical treatment of intracystic carcinoma of the breast.

BACKGROUND: Intracystic carcinoma of the breast is a type of breast cancer with favorable prognosis where cancer arises from the cystic wall. However, it is a relatively rare disease, and no general consensus has been reached on its definition, including pathogenesis, extramural invasion, and lymph node metastasis. METHODS: Six patients who underwent surgery at the Department of Surgery at Asahikawa Medical University are presented. In each patient, background factors, diagnosis, surgery, pathological diagnosis, and prognosis were investigated. RESULTS: Fine needle aspiration showed class V disease in three patients and class III disease in the other three, and lumpectomy was performed for class III patients. Three patients underwent breast-conserving surgery While extramural invasion was seen in three patients, lymph node metastasis was absent in all patients. CONCLUSION: When it is difficult to diagnose intracystic carcinoma of the breast by fine needle aspiration, active lumpectomy is necessary. Because extramural invasion and lymph node metastasis have been reported, it is necessary to carefully determine the range of excision and rationally perform lymph node dissection, such as sentinel node biopsy.

Mucoepidermoid carcinoma of the lung: a case report.

Mucoepidermoid carcinoma of the lung (MEC) is a tumor of low malignant potential of bronchial gland origin. MEC and adenoid cystic carcinoma are both considered to be salivary gland-type neoplasms. MECs are comparatively rare with an incidence of all lung cancers. We recently encountered a case of this type of lung cancer. A 60-year-old man was found to have an abnormal shadow in the left lower lung field on a regular check-up for lung cancer at his company. Chest radiography and CT revealed a mass shadow measuring 30 mm in diameter in the left lower lung field. Bronchoscopy revealed a protuberant tumor in the S9 bronchus, leading to a diagnosis of low-grade MEC by transbronchial lung biopsy. He underwent left lower lobe resection and mediastinal lymph node dissection using VATS. Tumor cells had a scattering of mucus-producing epithelial components in papillary growth of stratified squamous epithelia with anisokaryosis and minimal pleomorphism, indicating a diagnosis of MEC. Because the postoperative course was good and the tumor was low-grade, no adjuvant treatment was administered. The patient has had no signs of tumor recurrence for 9 months, to date, since resection of the tumor.

Role of treatment for solitary pulmonary nodule in breast cancer patients.

BACKGROUND: Metastatic pulmonary tumors secondary to breast cancer detected either before or after surgery are predominantly multiple and bilateral. However, in cases detected to have a solitary pulmonary nodule (SPN), determining whether the lesion represents a primary cancer, metastasis, or a benign pulmonary lesion can be difficult. MATERIALS AND METHODS: Between January 2000 and December 2009, we performed breast cancer surgery on 1,226 patients, of which 49 cases (3.9%) were detected to have pulmonary lesions before or after the surgery. In 14 of these patients, video-assisted thoracoscopic surgery was performed to remove a SPN. RESULT: Pathological examination of the resected specimens in these 14 cases revealed metastatic pulmonary tumor in 8 cases, primary lung cancer in 3 cases, and benign disease in 3 cases. While lobectomy was performed in one of these patients with metastatic pulmonary tumor, the remaining 7 underwent partial resection of the lung. The primary lung cancer was an adenocarcinoma in all 3 patients, and lobectomy plus mediastinal lymph node dissection was performed in these patients. The tumor grading based on pathological diagnosis was T1N0M0, p-Stage 1A in all 3 patients. The prognosis was good in the breast cancer patients in whom the metastatic lung tumor was a SPN. CONCLUSION: Evaluating the immunohistochemical cytokeratin profile and levels of the TTF-1 and GCDFP-15 of the lesion was useful when distinguishing between pulmonary cancer and metastatic pulmonary tumor. In addition, some patients exhibited changes in the biological properties of the metastatic tumor, and delete tumor resection by video-assisted thoracoscopic surgery can be useful for deciding the drug treatment strategy in some cases.

Ectopic thymoma presenting as a giant intrathoracic tumor: a case report.

Ectopic thymoma rarely presents as an intrathoracic tumor. We report a case of ectopic thymoma presenting as a giant right intrathoracic tumor that was treated with resection. The patient was a 50-year-old Japanese woman who presented with the chief complaint of chest pain. Detailed examination revealed a solid tumor measuring 15 × 10 × 8 cm in diameter, with a clear border. The Imaging findings suggested a solitary fibrous tumor, and surgery was performed. At surgery, the tumor was found to be adherent to the diaphragm, mediastinal pleura, and lower lobe of the lung, although it could be dissected with relative ease and was removed. Pathological diagnosis indicated a type B1 tumor with no capsular invasion according to the World Health Organization classification, and a diagnosis of Masaoka stage I thymoma was made. No continuity with the normal thymus tissue was seen, and the thymoma was considered to be derived from ectopic thymic tissue in the pleura.

Alpha-fetoprotein-producing primary lung carcinoma: a case report.

Alpha-fetoprotein (AFP)-producing lung adenocarcinoma is a rare type of lung cancer, with its characteristics not yet fully clarified. We recently encountered a case of this type of lung cancer. The patient was a 69-year-old man who consulted an internist with the chief complaint of epigastric pain. Chest X-ray and CT revealed a lobulated mass measuring 70 mm in diameter in the right lower lung field and a metastasis in the right hilar lymph nodes. Of the tumor markers, the serum AFP was elevated (4620 ng/ml), and the serum carcinoembryonic antigen and carbohydrate antigen 19-9 were also slightly elevated. Transbronchial lung biopsy revealed the diagnosis of lung cancer. Under thoracoscopic assistance, right lower lobectomy + mediastinal lymph node dissection was carried out. Immunostaining showed the tumor cells to be AFP-positive. The tumor was thus diagnosed as an AFP-producing lung adenocarcinoma. The patient followed an uneventful clinical course after the surgery, with serum AFP decreasing to the normal range by about 2 weeks after the surgery. As of this writing, no sign of tumor recurrence has been noted. This case is presented here with a review of the literature.

[Posterior mediastinal paraganglioma].

We report a case of 26-year-old man with a posterior mediastinal paraganglioma. Although he was asymptomatic, chest abnormal shadow was pointed out by the regular medical screening with chest X-rays. A chest computed tomography (CT) showed a left posterior mediastinal tumor with strong enhancement. He was referred to our hospital for surgery. We tried a video-assisted thoracic surgery (VATS) for resection of the tumor, but additional small thoracoscopy was necessary for control of bleeding. The patient's vital sign was stable at perioperative course. The histopathological examination revealed no evidence of malignancy, and a final diagnosis of paraganglioma was made. His postoperative course was uneventful, and is currently doing well without sign of recurrence. Because metastasis and/or local recurrence of paragangliomas is difficult to predict accurately only by histopathological finding, long-term follow-up is thought to be essential after surgery.