Pathological responses to low-dose irradiation and Pepleomycin in Oral squamous cell carcinoma are predictive of Locoregional control.

BACKGROUND: The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence. METHODS: We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato. RESULTS: Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively. CONCLUSIONS: The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.

Microscopic observation of chemical modification in sections using scanning acoustic microscopy.

A scanning acoustic microscope (SAM) calculates the speed of sound (SOS) through tissues and plots the data on the screen to form images. Hard tissues result in greater SOS; based on these differences in tissue properties regarding SOS, SAM can provide data on tissue elasticity. The present study evaluated whether tissue modifications, such as formalin fixation, periodic acid-Schiff (PAS) reactions and protein degradation, changed the acoustic properties of the tissues and whether SAM could be a useful tool for following chemical changes in sections. The fixation process was observable by the increased SOS. During the PAS reaction, the glycosylation of tissues was characterized by an increased SOS. Mucous or glycogen distribution was visualized and was found to be statistically comparable among lesions and states. Protease digestion by pepsin led to a decreased SOS. Tissue sensitivity to proteases varied due to the stage, cause and duration of inflammation or ageing. Changes in acoustic properties were more sensitive than those in optical histology. SAM facilitates the visualisation of the time course or distribution of chemical modifications in tissue sections, thus aiding their comparison among tissues. SAM may be an effective tool for studying changes such as protein cross-linkage, tissue repair and ageing.

Novel paired CD13-negative (MT-50.1) and CD13-positive (MT-50.4) HTLV-1-infected T-cell lines with differential regulatory T cell-like activity.

Adult T-cell leukemia/lymphoma (ATL) occurs after human T-cell leukemia virus type-1 (HTLV-1) infection with a long latency period exceeding several decades. This implies the presence of immune evasion mechanisms for HTLV-1-infected T cells. Although ATL cells have a CD4+CD25+ phenotype similar to that of regulatory T cells (Tregs), they do not always possess the immunosuppressive functions of Tregs. Factors that impart effective immunosuppressive functions to HTLV-1-infected cells may exist. A previous study identified a new CD13+ Treg subpopulation with enhanced immunosuppressive activity. We, herein, describe the paired CD13- (designated as MT-50.1) and CD13+ (MT-50.4) HTLV-1-infected T-cell lines with Treg-like phenotype, derived from the peripheral blood of a single patient with lymphoma-type ATL. The cell lines were found to be derived from HTLV-1-infected non-leukemic cells. MT-50.4 cells secreted higher levels of immunosuppressive cytokines, IL-10 and TGF-ß, expressed higher levels of Foxp3, and showed stronger suppression of CD4+CD25- T cell proliferation than MT-50.1 cells. Furthermore, the CD13 inhibitor bestatin significantly attenuated MT-50.4 cell growth, while it did not for MT-50.1 cells. These findings suggest that CD13 expression may be involved in the increased Treg-like activity of MT-50.4 cells. Hence, MT-50.4 cells will be useful for in-depth studies of CD13+Foxp3+ HTLV-1-infected cells.

Pulmonary mucosa-associated lymphoid tissue lymphoma forming a reversed halo sign from ground-glass opacity.

The reversed halo sign (RHS) has been associated with various pulmonary diseases. We report a rare case of pulmonary mucosa-associated lymphoid tissue lymphoma forming a RHS from a ground-glass opacity (GGO). A 73-year-old man was followed-up for the GGO on his computed tomography images, which gradually extended peripherally. During the fourth year of follow-up, the GGO significantly evolved into a well-demarcated, oval lesion, with interlobular and intralobular septal thickenings, and multiple air spaces were surrounded by a well-defined thin consolidative rim, called the RHS. A pathologic study of the specimen via transbronchoscopic biopsy revealed pulmonary mucosa-associated lymphoid tissue lymphoma.

Syphilitic aortitis: chronic left coronary ostial occlusion and aortic regurgitation with aortitis.

Before the discovery of penicillin, tertiary syphilis was the most common cause of thoracic aneurysms, but now cardiovascular syphilis is a clinical rarity in developed countries. We report a case of 69-year-old man who presented with sudden onset breathlessness that worsened insidiously for 2 months. Diagnosis of syphilitic aortitis was confirmed by laboratory findings, contrast computed tomography, echocardiography and coronary angiography. The patient underwent successful coronary artery bypass graft, aortic valve replacement and ascending aortic replacement. A high level of suspicion and awareness is needed for the diagnosis of the now rare disease.

Surgical outcomes and unique histological features of tonsils after tonsillectomy in adults with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

OBJECTIVES: Data on the adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome are scarce. European studies reported that unlike pediatric-onset PFAPA, tonsillectomy is ineffective for adult-onset PFAPA. The aims of this study were (1) to assess the response to tonsillectomy in a cohort of Japanese adult-onset PFAPA patients and (2) to evaluate the histologic appearance of tonsils in adult-onset PFAPA patients and to compare them with those of tonsils from age- and sex-matched controls with chronic tonsillitis. METHODS: In this retrospective cohort study, 5 adults with PFAPA and 15 controls who had undergone tonsillectomy were recruited. The size of the tonsil germinal centers was measured by hematoxylin and eosin staining, and the number and density of B and T lymphocytes in germinal centers were measured by immunohistochemistry, using CD3, CD4 and CD8 as T cell markers and CD20 as B cell marker. RESULTS: All patients had complete remission of the symptoms after surgery. PFAPA patients had significantly smaller germinal center areas than controls. The number and density of CD8+ cells in germinal centers were significantly lower in tonsils from PFAPA compared with controls. No differences were found between the two groups in CD3+, CD4+, and CD20+ cells. These results are compatible with the tonsillar features of pediatric-onset PFAPA. CONCLUSION: Our report demonstrates that tonsillectomy might be effective for adult-onset PFAPA and that tonsils of adult- and pediatric-onset PFAPA share the same histological features. These results suggest that the pathogenic mechanisms of adult- and pediatric-onset PFAPA are identical.

A Case of Adult-Onset Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome Responsive to Tonsillectomy in Japan.

Adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a rare condition, having been reported in only three patients in Japan till date. While almost all pediatric PFAPA patients respond well to tonsillectomy, some European studies have reported that tonsillectomy may be ineffective for adult-onset PFAPA. All the Japanese patients with adult-onset PFAPA had been treated orally so far (cimetidine with or without prednisone), instead of tonsillectomy. We reported a case involving a 37-year-old Japanese man with PFAPA syndrome who presented with a history of febrile episodes associated with pharyngitis, cervical adenitis, and aphthous stomatitis for one year. The patient had been undergoing oral medication therapy without any significant improvement. Tonsillectomy was performed for the patient, and complete resolution of PFAPA was achieved. Our experience suggests that a tonsillectomy is a viable option for the treatment of adult-onset PFAPA.

CD151 confers metastatic potential to clear cell sarcoma of the soft tissue in animal model.

Cluster of differentiation 151 (CD151) is a potent therapeutic target for regulating tumor metastasis. In the present study, the role of CD151 in clear cell sarcoma of soft tissue was examined using a xenoplanted tumor model, which had high rates of metastasis. A clear cell sarcoma cell line, HS-MM, which was transplanted to the aponeuroses of the thighs, the most affected sites of human clear cell sarcoma, exhibited robust lymphatic invasion and nodal metastasis in SCID-beige mice. Serial in vivo passaging of peritoneally disseminated tumor cells accelerated the metastatic activity, which was accompanied by increased CD151 expression, and were designated as HS-MMhigh. Notably, inoculation of anti-CD151 antibody significantly suppressed the lymphatic invasion, peritoneal dissemination and distant metastasis of the present clear cell sarcoma model without affecting local tumor growth at the transplantation site. Small interfering RNA (siRNA)-mediated downregulation of CD151 did not alter cell proliferation, but significantly inhibited Matrigel invasion activity of HS-MMhigh cells. Downregulation of CD151 impaired matrix metalloproteinase-9 activity and phosphorylation of SMAD3 protein in HS-MMhigh cells. The present results suggest that CD151 may contribute to invasion and metastasis of clear cell sarcoma of soft tissue. Therefore, CD151 may serve as a potent target to regulate metastasis of clear cell sarcoma.

Therapeutic potential of CPI-613 for targeting tumorous mitochondrial energy metabolism and inhibiting autophagy in clear cell sarcoma.

Clear cell sarcoma (CCS) is an aggressive type of soft tissue tumor that is associated with high rates of metastasis. In the present study, we found that CPI-613, which targets tumorous mitochondrial energy metabolism, induced autophagosome formation followed by lysosome fusion in HS-MM CCS cells in vitro. Interestingly, CPI-613 along with chloroquine, which inhibits the fusion of autophagosomes with lysosomes, significantly induced necrosis of HS-MM CCS cell growth in vitro. Subsequently, we established a murine orthotropic metastatic model of CCS and evaluated the putative suppressive effect of a combination of CPI-613 and chloroquine on CCS progression. Injection of HS-MM into the aponeuroses of the thigh, the most frequently affected site in CCS, resulted in massive metastasis in SCID-beige mice. By contrast, intraperitoneal administration of CPI-613 (25 mg/kg) and chloroquine (50 mg/kg), two days a week for two weeks, significantly decreased tumor growth at the injection site and abolished metastasis. The present results imply the inhibitory effects of a combination of CPI-613 and chloroquine on the progression of CCS.

Two Cases of Cartilaginous Choristoma-Not Chondroma of the Bony External Auditory Canal.

The presence of a cartilaginous mass on the bony external auditory canal is an unusual finding. Currently, two different diagnoses have been used to describe this type of mass: chondroma and cartilaginous choristoma. There is currently no consensus on which diagnosis is appropriate for this type of lesion. Choristoma is defined as a tumor-like growth of normal tissue occurring in an abnormal location. Histological examination alone cannot be used to distinguish between cartilaginous choristoma and chondroma, as both lesions comprise normal mature hyaline cartilage. To diagnose a mass as cartilaginous choristoma on the bony external auditory canal, it is necessary to confirm that it does not originate from the underlying periosteum. Here, we present the cases of two patients with typical cartilaginous masses on the bony external auditory canal, in which the surgical findings showed that the masses were not in contact with the underlying periosteum, indicating that cartilaginous choristoma-not chondroma-is an appropriate diagnosis for these mass lesions. The clinical findings (characteristic appearance and location) reported here may aid clinicians in the diagnostic and surgical management of these cartilaginous masses.

Primary synovial sarcoma of the stomach--a case report and review of the literature.

Synovial sarcoma (SS) is a mesenchymal spindle cell tumor which displays variable epithelial differentiation. It commonly arises around the major joints or tendon sheaths in young adults, but is not commonly seen in the stomach. We experienced a case of primary gastric SS. The patient is a 22-year-old male, who presented with epigastric pain. Upper endoscopy showed an ulcer of 25 mm in diameter with marginal elevation on the posterior mid-gastric body. Biopsy of the ulcer base showed monotonous proliferation of small spindle-shaped cells on HE-stain. On immunohistochemical staining, these cells were positively stained with vimentin, cytokeratin, epithelial membrane antigen, and CD99, but were negative for KIT, CD34, desmin, and S-100 protein. These findings were compatible with SS of monophasic type. Diagnosis of primary gastric SS was made because there were no other primary lesions, nor metastatic lesions. The wedge resection was performed. Reverse transcriptase polymerase chain reaction (RT-PCR), using the RNA from frozen neoplastic tissue of the resected specimen, detected a fusion gene called SYT-SSX1, specific for SS. Though SS arising in the stomach is rare, it should be considered in the differential diagnosis of KIT-negative gastric spindle cell tumor.