Recurrent cementoblastoma with multifocal growth and cellular atypia: a case report.

BACKGROUND: Cementoblastoma is a rare odontogenic tumor characterized by the formation of osteocementum-like tissue on a tooth root directly by neoplastic cementoblasts. Although it is categorized as benign, it has a high potential for growth with a certain degree of recurrence risk. However, there are only a few studies describing the features of recurrent cementoblastoma. The diagnosis of recurrent cementoblastoma is challenging not only due to its cytological atypia but also because of its large size and multicentric growth pattern. These characteristics suggest a potential for malignancy. CASE PRESENTATION: A 29-year-old woman was transferred to our university dental hospital complaining of swelling of the right mandible. She had a history of enucleation of cementoblastoma associated with the third molar of the right mandible. Five years after the initial treatment, imaging demonstrated well-circumscribed multicentric radiopaque lesions in the same area. Histologically, the lesion consisted of osteocementum-like tissue rimmed with polygonal or plump tumor cells. Several cells were large epithelioid cells with bizarre nucleoli, which may be reminiscent of malignant tumors. Otherwise, there were no apparent malignant findings, including proliferative activity or atypical mitotic figure. Besides, tumor cells were positive for c-FOS, a marker of osteoblastoma and cementoblastoma. Eventually, the patient was diagnosed with recurrent cementoblastoma. CONCLUSIONS: Pathological analyses of this case suggested that the recurrent event in the cementoblastoma altered its growth pattern and tumor cell shape. Moreover, in the case of enucleation surgery, long-term follow-up is important because there is some recurrent risk of cementoblastoma, although it is not high.

Eosinophilia in the muscle layer of the esophagus and the urinary bladder in a Multiple System Atrophy patient with dysphagia and dysuria.

Multiple system atrophy (MSA) is a spinocerebellar degenerative disease characterized by cerebellar ataxia, parkinsonism, and autonomic failure. A 75-year-old woman who had suffered from dysphagia and dysuria under a diagnosis of probable MSA with predominant cerebellar ataxia underwent autopsy. Eosinophilia was seen extensively in the muscle layer of the esophagus and urinary bladder. Eosinophilic infiltration to the esophagus was localized in the smooth muscle layer and could be considered as "eosinophilic esophageal myositis" identified in patients with nutcracker esophagus and jackhammer esophagus. Dense eosinophilia was present within the smooth muscle layer of the urinary bladder along with muscle fiber degeneration. We suspected a neuropathic etiology associated with MSA as the cause of the histological changes in the esophagus and urinary bladder; however, the possibility that some other disease might also have been responsible for the eosinophilic infiltration of the muscle layer cannot be denied. To our knowledge, this is the first report showing localized eosinophilia in the muscle layers of the esophagus and urinary bladder in the same patient. Although localized eosinophilia in visceral muscle has not been understood well, our case suggests the possibility that it is a feature of functional motility disorders and may have a neuropathic etiology.

A case of mixed adenoneuroendocrine carcinoma of the pancreas: Immunohistochemical analysis for histogenesis.

RATIONALE: Tumors with multiple histological features, such as adenocarcinomas and neuroendocrine carcinomas, were included as a new category of neuroendocrine carcinomas in the 2010 World Health Organization classification. We recently experienced a rare case of a pancreatic carcinoma with both adenocarcinoma and neuroendocrine carcinoma components, a so-called mixed adenoneuroendocrine carcinoma. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old man was referred to our hospital with obstructive jaundice. Contrast-enhanced computed tomography images indicated a tumor located at the pancreatic head measuring 3.0 × 2.5 cm in diameter and invading the common bile duct. Cytological examination of the bile juice obtained by endoscopic retrograde cholangiopancreatography revealed adenocarcinoma cells. Pancreaticoduodenectomy was performed safely as radical resection. INTERVENTIONS: Microscopically, the resected tumor consisted of tightly intermingled adenocarcinoma and neuroendocrine carcinoma components. On the immunohistochemical examination, p53 was ubiquitously positive in both components, whereas chromogranin A, synaptophysin and neuron-specific enolase, neuroendocrine markers, were limited to the neuroendocrine carcinoma component. OUTCOMES: Thus, such features of both adenocarcinoma and neuroendocrine carcinoma observed microscopically and immunohistochemically seemed to indicate a composite tumor. LESSONS: The findings of this case suggest that adenocarcinoma and neuroendocrine carcinoma may be derived from a single cancer stem cell.

Pleural vasculitides of microscopic polyangiitis with asbestos-related plaques.

A 69-year-old man who had been exposed to asbestos for approximately 40 years presented with the complaint of fever and pleuritic chest pain on the right side on deep inspiration. Chest X-ray films showed pleural effusion in the right side. Initial antibiotic treatment was ineffective. The hyaluronic acid level was high in the pleural effusion but no malignant mesotheliomal cells were seen with blind pleural biopsy. Blood chemistry showed a remarkable high titer of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and open renal biopsy suggested crescentic glomerulonephritis. The precise pathological examination on the pleura obtained by the open pleural biopsy showed vasculitides and plaque leading to diagnosis of microscopic polyangiitis (MPA). This is a rare case of MPA seen in the pleural arteries.

Pathological and molecular biological approaches to early mesothelioma.

Malignant mesothelioma is an asbestos-related malignancy that arises primarily from mesothelial cells on the serosal surfaces of the pleural, peritoneal, and pericardial cavities. Malignant pleural mesothelioma (MPM) is most common, and its incidence is dramatically increasing worldwide as a result of widespread use of asbestos. Morphological discrimination between MPM and reactive mesothelial hyperplasia is difficult, and the most reliable pathological criterion for malignancy is mesothelial proliferation invading deeply into subpleural adipose tissues. To establish radical cure of MPM, it is crucial to find early-stage MPM of epithelial type, in which mesothelial proliferation is localized on the serosal surface of parietal pleura or limited within the submesothelial fibrous tissues of parietal pleura. The initial clinical presentation for patients with MPM is frequently dyspnea and/or chest pain due to large pleural effusion, and cytological analysis of pleural effusions is valuable to find patients with early-stage MPM of epithelial type. Recently, cytological features of MPM in pleural effusion, molecular markers for MPM, and genetic alternations of MPM have been reported. In this review, we discuss major issues on pathological and molecular biological approaches for diagnosis of early-stage MPM of epithelial type.

Establishment of a cell line from a Japanese patient useful for generating an in vivo model of malignant pleural mesothelioma.

Malignant pleural mesothelioma is a refractory tumor with increasing incidence. In the present study, we established six mesothelioma cell lines possessing two allele deletions of the p16(INK4A) gene and one allele deletion of the neurofibromatosis type 2 gene, MM16, MM21, MM26, MM35, MM46 and MM56, from pleural effusion fluids or surgically resected tumors of Japanese patients. MM21, MM26 and MM46 cells failed to develop tumors in BALB/c-nude mice following subcutaneous inoculation. MM16 and MM35 cells slowly generated tumors at the site of subcutaneous inoculation in BALB/c-nude mice, but lost the expression of mesothelioma-related markers such as calretinin, D2-40 and Wilms' tumor 1 in the subcutaneous tumors. On the other hand, MM56 cells rapidly generated tumors with the expression of calretinin and D2-40 in BALB/c-nude mice following subcutaneous inoculation. In addition, orthotopic implantation of MM56 cells into BALB/c-nude mice developed diffusely growing thoracic tumors by 3 weeks after implantation. Pleural effusions were observed in these mice 4 weeks after implantation. Thoracic tumors invaded aggressively into the chest wall 5 weeks after implantation and often metastasized into the lung, rib, peritoneum and pericardial cavity. On the pleural surface, MM56 cells were growing as single or multiple cell layers with the reactive mesothelium of recipient mice. These results indicate that MM56 cells can behave in a manner characteristic of human malignant pleural mesothelioma in the thoracic cavity of BALB/c-nude mice. The in vivo model using MM56 cells may be useful for studying the biological behavior of malignant pleural mesothelioma and developing its diagnostic and therapeutic strategies.

CD44 expression is related to poor prognosis of hypopharyngeal squamous cell carcinoma.

CONCLUSIONS: CD44 expression in hypopharyngeal squamous cell carcinomas (SCCs) is closely associated with poor prognosis for patients. CD44 may serve as a prognostic marker for hypopharyngeal SCCs. OBJECTIVES: CD44, an adhesion molecule binding to extracellular matrix, is believed to participate in the progression of malignancies. To clarify the role of CD44 in the progression of hypopharyngeal SCCs, we examined CD44 expression in relation to clinical parameters in hypopharyngeal SCCs. METHODS: Biopsy specimens of hypopharyngeal SCCs were collected from 40 untreated patients, and their CD44 expression was examined immunohistochemically. Hypopharyngeal SCCs were classified into two groups: CD44-low SCCs comprising < 50% CD44-positive tumor cells and CD44-high SCCs comprising ≥ 50% CD44-positive tumor cells. The relation between CD44 expression and various parameters (clinical T and N stages, distant metastasis, and pathological T and N stages) was analyzed by Fisher's exact test. The relation between CD44 expression and the 5-year disease-free survival (DFS) rate was also analyzed by log rank test. RESULTS: The CD44 expression in hypopharyngeal SCCs was related to pathological N stage, but not to clinical T and N stages and pathological T stage, of the patients. Distant metastasis during the follow-up occurred more frequently in patients with CD44-high SCCs than those with CD44-low SCCs. The 5-year DFS was significantly lower in the former than in the latter.

Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium.

Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.

Early uptake and continuous accumulation of thallium-201 chloride in a benign mixed tumor of soft tissue: case report.

A case of benign mixed tumor of the soft tissue in a 64-year-old Japanese male is presented. He noticed a painless, elastic hard mass sized 3 cm in the right knee, which gradually grew larger and harder in the last 5 years. Magnetic resonance imaging demonstrated a mass lesion embedded in the subcutaneous tissue with low and high signal intensity at T1- and T2-weighted images, respectively. Tl-201 scintigraphy showed an early uptake of Tl-201 within the lesion at 10 minutes after injection, which was slightly decreased but still continued at 2 hours later. The patient underwent a resection of tumor, and the pathological diagnosis was a benign mixed tumor of soft tissue without high vascularity, characterized by histological features similar to pleomorphic adenomas in the salivary glands. Immunohistochemical study proved expression of Na+/K+-ATPase of tumor cells. Overexpression of Na+/K+-ATPase of the tumor might be responsible for the early uptake of Tl-201, and poor vascular structure in this tumor might lead to continuous accumulation. The Tl-201 scintigraphic features of mixed tumor of soft tissue are assessed to resemble those of malignant soft tissue tumors.

CD74 is a novel prognostic factor for patients with pancreatic cancer receiving multimodal therapy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is still one of the most fatal cancers, although its prognosis has improved recently with the introduction of multimodal therapy. To further develop effective treatment for PDAC, establishment of prognostic indicators for patients receiving multimodal therapy is essential. METHODS: Sixty-eight patients receiving curative extended resection combined with preoperative chemoradiation and postoperative chemotherapy for primary PDAC were selected. Immunohistochemistry using anti-CD74 antibody on paraffin-embedded tissue samples was performed, and cases were divided into two groups according to the ratio of CD74-positive cells: expression level I, CD74-positive cells <70%; level II, CD74-positive cells >or=70%. The correlation of CD74 expression level with clinicopathological features and overall survival was evaluated. RESULTS: Forty-seven (69.1%) and 21 (30.9%) patients showed level I and II CD74 expression, respectively. Patients with level II CD74 expression showed a higher rate of lymphatic permeation (P = 0.04) and perineural invasion (P = 0.01) compared with those with level I expression. Patients with level I CD74 expression had a significantly better survival rate than those with level II (P = 0.003). Among the patients with pathological tumor-node-metastasis stages I and II, those with level I CD74 expression showed a significantly better prognosis than those with level II (P = 0.006). Multivariate analysis revealed CD74 expression level and vascular permeation of carcinoma as independent prognostic indicators. CONCLUSIONS: CD74 expression proved as a useful prognostic indicator for PDAC treated with multimodal therapy.