Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

BACKGROUND: At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies. RESULTS: The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group. CONCLUSIONS: CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival.

Inflammatory pseudotumor in head and neck.

BACKGROUND: Inflammatory pseudotumor (IPT) is a tumefactive lesion characterized by fibroblastic proliferations and a prominent inflammatory component. It behaves as a locally benign or aggressive lesion, clinically and radiologically mimicking a neoplastic process. Numerous entities can be diagnosed as IPT, from reactive lesions to true neoplasms. The diagnosis of IPT requires further elaboration, and IPT should be distinguished from other similar entities such as inflammatory myofibroblastic tumor and IgG4-related sclerosing disease. CASE SUMMARY: We report two cases of IPT arising from the head and neck region. One occurred at the orbit and the other at the parapharyngeal space. Histologically, they showed aggregates of myofibroblasts and inflammatory cells. Immunohistochemically, the number of IgG4-positive cells was less than 40% of the number of IgG positive cells, and the myofibroblastic cells were negative for anaplastic lymphoma kinase. The diagnosis was IPT/not otherwise specified. One patient was treated by systemic administration of corticosteroid and had good response. The other, who was treated by local administration of corticosteroid, partially responded and is currently stable with limited disease. DISCUSSION: IPT has been reported to occur in various anatomical sites, most commonly in the lungs. The incidence in the head and neck area is extremely rare. Treatment of IPT is controversial and may involve corticosteroids or surgical resection, or both. Other chemotherapeutic agents and radiotherapy may be considered in steroid-resistant patients. The pathological subtype, safety of resection, and safety of corticosteroid use must be included in the decision-making process for treatment.

Diagnosis and management of extracranial head and neck schwannomas: a review of 27 cases.

Objectives. Clinical records of 27 patients with extracranial head and neck schwannoma were retrospectively reviewed. Methods. Ultrasonography (US) was performed in all cases. Seven patients underwent CT. Twenty-five patients underwent MRI. Fine needle aspiration cytology (FNAC) was performed for 12 of the 27 patients. Clinical history, surgical data, and postoperative morbidity were analyzed. Results. The images of US showed a well-defined, hypoechoic, primarily homogeneous solid mass. At CT, only one of 7 cases (14%) was able to suggest the diagnosis of schwannoma. At MRI, twenty of 25 cases (80%) suggested the diagnosis of schwannoma. Only three of 12 cases (25%) displayed a specific diagnosis of schwannoma rendered on FNAC. The distribution of 27 nerves of origin was 10 (37%) vagus nerves, 6 (22%) sympathetic trunks, 5 (19%) cervical plexuses, 3 (11%) brachial plexuses, 2 (7%) hypoglossal nerves, and 1 (4%) accessory nerve. Complete tumor resection was performed in 11 patients, and intracapsular enucleation of the tumor was performed in 16 patients. The rate of nerve palsy was 100 (11/11) and 31% (5/16). Conclusions. MRI is sensitive and specific in the diagnosis of schwannoma. Intracapsular enucleation was an effective and feasible method for preserving the neurological functions.

Surgical management of malignant tumors of the trachea: report of two cases and review of literature.

Malignant neoplasms occurring from the trachea are extremely rare. Therefore, their clinical characteristics and surgical results have not been thoroughly discussed. These tumors are often misdiagnosed and treated as bronchial asthma or chronic obstructive pulmonary disease. It is critically important to probe the cause-effect relationship between the medical presentations and the clinical diagnosis. In this report, two cases of tracheal malignancy suffering from dyspnea due to obstruction of the proximal trachea are described, and a review of the literature is presented.

Small cell carcinoma of the tonsil treated with irinotecan and Cisplatin: a case report and literature review.

We report a rare case of extrapulmonary small cell carcinoma arising in the palatine tonsil treated by combined chemotherapy with irinotecan/cisplatin following irradiation therapy. This chemotherapy regimen was recently found to be effective for small cell lung carcinoma. Our case is the first report of combined irinotecan/cisplatin chemotherapy to treat extrapulmonary small cell carcinoma of the oropharynx.

Close correlation between CXCR4 and VEGF expression and their prognostic implications in nasopharyngeal carcinoma.

The CXCL12/CXCR4 pathway, which is involved in biological phenomena such as inflammation, lymphoid homing and regeneration, may play an important role in tumor progression and distant metastasis, especially in organ-selective metastasis. In addition, the CXCL12/CXCR4 pathway has been reported to regulate tumor angiogenesis. In this study, we examined the immunohistochemical expression of CXCR4 and vascular endothelial growth factor (VEGF) in nasopharyngeal carcinoma. CXCR4 and VEGF mRNAs were also assessed by real-time reverse transcription-polymerase chain reaction. Overexpression of CXCR4 and VEGF was observed in 41 (53.9%) and 30 (39.5%) of 76 tumors, respectively. There was a significant positive correlation between immunohistochemical CXCR4 and VEGF expression (p=0.0339). Additionally, immunohistochemical CXCR4 expression was associated with CXCR4 mRNA expression, and immunohistochemical VEGF expression was associated with VEGF mRNA expression (p=0.0040 and p=0.0476, respectively). Furthermore, patients with VEGF-positive tumors had a significantly worse prognosis than patients with VEGF-negative primary tumors (p=0.0044). Our findings suggest that the expression of CXCR4 and VEGF is associated with metastatic progression, and that VEGF expression is a valuable prognostic marker in nasopharyngeal carcinoma.

Aggressive invasive micropapillary salivary duct carcinoma of the parotid gland.

The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.

A case of primary Hodgkin's lymphoma of the parotid gland.

We report an extremely rare case (sixth reported case) of primary Hodgkin's lymphoma (HL) (mixed cellularity type) of the parotid gland. A 14-year-old man was referred to our hospital for evaluation of a parotid mass. Although the initial aspiration cytology was highly suggestive of HL, the confirmatory diagnosis obtained by open biopsy was non-specific lymphadenitis. Consequently, the patient was observed without any additional treatment. Because the mass continued to increase in size, we performed a total parotidectomy which led to the diagnosis of mixed cellularity HL. This case suggests that the specimen taken during open biopsy may have been too small (about 1 cm3) to detect the presence of Reed-Sternberg giant cells, which is essential for the diagnosis of HL. Therefore, although primary HL of the parotid gland is extremely rare, adequate tissue sampling of a clinically suspicious parotid mass will be required for the diagnosis of HL.

Pigmented villonodular synovitis with chondroid metaplasia, resembling chondroblastoma of the bone: a report of three cases.

We herein describe three cases of pigmented villonodular synovitis with chondroid metaplasia. Two cases involved the temporomandibular joint, whereas the remaining one case occurred in the hip joint. Histologically, the tumors showed a villous pattern and were mainly composed of histiocyte-like cells and scattered osteoclast-like multinucleated giant cells, accompanied by chondroid areas with occasional lace-like calcification. These features resembled those of chondroblastoma of the bone, with the exception of the villous pattern. The histiocyte-like cells showed positive immunoreactivity for CD68, whereas they were negative for S-100 protein. Some of the previously reported cases of chondroblastoma in the temporal bone may have actually been cases of pigmented villonodular synovitis with chondroid metaplasia. When histologically chondroblastoma-like lesions involve the temporal bone or temporomandibular joint, the possibility of pigmented villonodular synovitis with chondroid metaplasia should also be considered, in addition to chondroblastoma of the bone. The correlation between this lesion and synovial chondromatosis remains uncertain.