High-grade sinonasal carcinomas and surveillance of differential expression in immune related transcriptome.

The skull base is the location of a wide variety of malignant tumors. Among them is sinonasal undifferentiated carcinoma (SNUC), a highly aggressive sinonasal neoplasm that was recently reclassified into subgroups of high-grade carcinomas with unique genomic events (e.g., SMARC-deficient carcinoma, nuclear protein in testis NUT carcinoma). Other high-grade carcinomas in this location are neuroendocrine carcinomas, sinonasal adenocarcinomas, and teratocarcinosarcomas. Given the rarity of these tumors, little transcriptomic data is available. The aim of this study was to characterize the immune-oncology gene expression profile in SNUC and other high-grade sinonasal carcinomas. Next-generation sequencing was performed in 30 high-grade sinonasal carcinoma samples using the HTG EdgeSeq Precision Immuno-Oncology Panel. Ingenuity pathway analysis was performed to understand the immunobiology, signaling, and functional perturbations during tumor development. The samples were divided into 3 groups: 21 SNUCs and SMARC-deficient sinonasal carcinomas; 5 high-grade neuroendocrine carcinomas (HGNECs), with small cell and large cell variants; and 4 high-grade sinonasal carcinomas (HGSNCs) of mixed histology (1 NUT carcinoma, 1 teratocarcinosarcoma, and 2 sinonasal adenocarcinomas). PRAME and ASCL1 emerged as upregulated transcripts with strong protein validation for SNUC and HGNEC; other upregulated candidates EZH2 and BRCA1 offer consideration for alternative targeted therapy, and downregulation of major histocompatibility complex molecules and chemokines represent another hurdle in the development of effective immunotherapy. This immune-oncology gene expression analysis of 3 groups of high-grade sinonasal carcinoma with emphasis on SNUC identified a number of differentially expressed transcripts reflecting effects on tumorigenesis. Identification of immune pathways should be further investigated for possible integration of immunotherapy into a multidisciplinary approach to these cancers and personalized treatment.

IgG4-related plasma cell granuloma of the maxillary sinus: A report of 2 cases.

We report 2 rare cases of IgG4-related plasma cell granuloma of the maxillary sinus. Histologically, both lesions were characterized by severe lymphoplasmacytic infiltration. In 1 case, fibrous sclerosis and obliterative arteritis were observed. Immunohistochemical study demonstrated that IgG4-positive cells comprised more than 40% of the IgG-positive plasma cells. Moreover, the serum IgG4 level was elevated in both cases. A good responsiveness to steroid therapy has been seen in IgG4-related disease. From a therapeutic perspective, it is important to recognize IgG4-related plasma cell granuloma.

Frequency, suppressive capacity, recruitment and induction mechanisms of regulatory T cells in sinonasal squamous cell carcinoma and nasal inverted papilloma.

BACKGROUND: Sinonasal squamous cell carcinoma (SSCC) and nasal inverted papilloma (NIP) represent the predominant type of malignant and benign tumors in sinonasal tract, respectively. CD4+ CD25+ Foxp3+ natural regulatory T (Treg) cells might play critical role(s) in the suppression of anti-tumor immune response and thus shed light on tumor progression from benign to malignant. OBJECTIVE: This study aimed to evaluate the frequency and suppressive capacity of Treg cells in SSCC compared to NIP and further to explore the underlying mechanisms. PATIENTS AND METHODS: Frequencies of Treg, Th1 and Th2 cells were evaluated by flow cytometry in tissue homogenate and peripheral blood from 31 SSCC patients, 32 NIP patients and 35 normal controls. Treg cells were tested for regulatory function by co-culture with effector T cells. CCR4 and its ligands, CCL22 and CCL17, were analyzed by flow cytometry and Luminex, respectively. The chemoattractant properties of CCR4/CCL22 and CCR4/CCL17 for Treg cells were assessed using the Boyden chamber technique, to elucidate the potential mechanisms of Treg recruitment in tumor microenvironment. Treg cells induction via TGF-ß was assessed with transwells after local CD4+ Foxp3+ T cells were assessed by immunohistochemistry and TGF-ß concentration was measured by Luminex. RESULTS: Tumor-infiltrating Treg cells increased significantly from normal to NIP to SSCC (P ≤ 0.001 for normal vs. NIP and P = 0.004 for NIP vs. SSCC). Significantly elevated frequency and enhanced suppression capacity of circulating Treg cells in SSCC were detected compared to NIP and healthy controls, concomitant with Th1 decrease and Th2 increase. Apparently increased CCL22 attracted CCR4-expressing Treg cells to tumor microenvironment in SSCC, compared to NIP. SSCC produced significantly more TGF-ß than NIP and thus possessed greater potential for Treg cell induction. CONCLUSION: Frequency and suppressive capacity of Treg cells enhanced with progression of malignancy from NIP to SSCC. Circulating Treg cells were recruited to tumor tissue via CCR4/CCL22 signalling, whereas tumor-synthesised TGF-ß contributed to induction of peripheral Treg cells.

Inflammatory myofibroblastic tumor of the maxillary sinus related with pulp necrosis of maxillary teeth: case report.

Inflammatory myofibroblastic tumor (IMT) is a benign lesion composed of myofibroblasts accompanied by varying numbers of inflammatory cells. Various pathogenetic factors have been proposed, but the etiology of most IMTs remains unknown. This article presents a case of IMT occurring in the left maxillary sinus. A 24-year-old man complained of throbbing pain in the maxillary left molars and swelling of the left cheek. His maxillary left second molar was diagnosed as pulp necrosis and root canal treatment performed. After that, his symptoms continued and he was referred to the Department of Otolaryngology. Computerized tomography disclosed compact soft tissue masses in the left maxillary sinus with obstruction of maxillary ostium. Under general anesthesia, the lesions were fully excised. Histopathologically, the lesions were composed of plump or spindled myofibroblasts. Cells were immunoreactive for smooth muscle actin and ß-catenin, and were negative for ALK1, CD34, and EMA. The diagnosis was IMT of left maxillary sinus. Although it is very rare, IMT should be included as a differential diagnosis in patients with compact masses in maxillary sinus.

[Change of reactive small round cell infiltration in the stroma after pre-operative 8 Gy irradiation using treatment to maxillary sinus carcinoma with Kitasato method and prognosis according to the change].

PURPOSE: In this paper, we report the results of studying the degree of reactive small round cell infiltration in the stroma as a prognostic indicator of maxillary sinus carcinoma treated with the Kitasato method and the effect of preoperative irradiation at 8 Gy on infiltration in the stroma. SUBJECTS: Out of 74 patients who had been treated with this method in the 27 years from 1976 to 2002, the following patients were enrolled in this study: (1) 17 patients from whom tissue specimens could be obtained with biopsies or probe antrotomies before preoperative irradiation, and (2) 40 patients from whom tissue specimens could be obtained after preoperative irradiation including those who survived five years and who died of a specific cause. METHOD: We classified the pattern of distribution of small round cell infiltration in the stroma into three degrees. (1) Stromal infiltration was compared before and after the operation to recognize the prognosis for each patient based on the pattern of distribution of small round cell infiltration in the stroma. (2) The correlation between the degree of stromal infiltration and prognosis was studied statistically. RESULTS: (1) Both the patients with increased stromal infiltration and those postoperatively preserving a preoperative score of 2+ with irradiation at 8 Gy had a good prognosis. (2) The five-year survival rate for patients was significantly higher in those with a score of 2+ for their tissue specimens. CONCLUSION: The Kitasato treatment method is effective and improves the QOL of patients with maxillary sinus carcinoma. The prognosis was good in the patients with increased or preserved stromal infiltration. The low-dose irradiation and chemotherapy used in combination seemed to be biological response modifiers.

Isolation and characterisation of adenoid squamous carcinoma cells highly producing SCC antigen and CEA from carcinoma of the maxillary sinus.

A serially transplantable adenoid squamous carcinoma tumour line (SCCMM) derived from carcinoma of the maxillary sinus of a 56-year-old male with high serum levels of SCC antigen (SCC-Ag) and carcinoembryonic antigen (CEA) was established in athymic nude mice. Nude mouse tumours produced by transplantation of operated material showed similar histological features to those of the original tumour and expression of SCC-Ag and CEA immunohistochemically. In addition, SCC-Ag and CEA in sera of tumour-bearing nude mice were detected at high levels in proportion to the relative tumour weight. The primary cultured tumour cells demonstrated the expression of SCC-Ag and CEA and the production of these antigens into culture medium. The serum levels of these tumour antigens were decreased concomitant with tumour regression by antitumour drug administration. Therefore, this tumour line and its cultured cells could provide a useful model for investigation of the relationship between tumour growth and expression of these tumour antigens.

[Interleukin 10 and chronic vitritis in a case of ocular lymphoma]. / Interleukine-10 et vitrite chronique dans un cas de lymphome oculaire.

The authors report on a 46 year-old patient who presented with a chronic unilateral vitritis. A diagnosis of cerebral lymphoma was made 4 years earlier and a maxillary sinus recurrence was treated with chemotherapy and radiotherapy. A vitrectomy was performed and the level of Interleukin-10, a lymphoma cells growth factor, was found very high, giving a clue for the lymphomatous cause of the vitritis.

Low doses of anticancer drugs increase susceptibility of tumor cells to lysis by autologous killer cells.

Pretreatment of squamous cell carcinoma (SCC) cells from four patients with low doses of cisplatin, carboplatin or 5-fluorouracil increased the susceptibility to lysis by autologous killer cells in vitro. Exposure of two SCC cell lines to low doses of these drugs increased the cell surface expression of both HLA class I and intercellular adhesion molecule-1 (ICAM-1). HLA class II, neural cell adhesion molecule and B7 were not expressed on the cell surface before or after such treatment. The results suggest that these drugs increase the susceptibility of tumor cells to autologous cell-mediated cytotoxicity, at least in part, by enhancing the expression of HLA class I and ICAM-1.

Unusual case of plasma cell tumor with monoclonal gammopathy of the sino-nasal cavity and clavicular bone.

A rare case of extramedullary plasmacytoma in the sino-nasal cavity is presented. During a prolonged clinical course, the tumor has recurred several times after irradiation, chemotherapy and surgery, and presented in the clavicular bone as well. Immunohistochemical staining of each tumor showed IgA kappa phenotype, and immunoelectrophoresis of the serum showed overproduction of IgA with kappa light chains. Although an elevation of serum IgA persists, the patient has remained well without evidence of overt multiple myeloma.

[Sensitivity test to chemotherapeutic agents and cytotoxicic test against immuno-effecter cells of established malignant fibrous histiocytoma cell line].

UNLABELLED: A cell line was established from a patient with malignant fibrous histiocytoma, which had originated in the maxillary sinus. Using this cell line, sensitivity to chemotherapeutic agents and cytotoxicity against various immunoeffecter cells were tested. RESULTS: This MFH cell line was sensitive in some degree to adriamycin, 5-fluorouracil, cisplatin, peplomycin, and methotrexate at high doses, but insensitive to mitomycin-C, vincristine and cyclophosphamide. Furthermore, this cell line showed no sensitivity to cytolytic cytokines, such as tumor necrosis factor-alpha and interferon-gamma. Lymphokine activated killer (LAK) cells and lymphokine activated tumor infiltrating lymphocytes (LA-TIL), induced by culture of peripheral blood lymphocytes and TIL respectively with rIL-2 showed high NK and LK activities and remarkable anti-autologous tumor ability.

[Orofacial lymphomas in seropositive patients manifesting the type I human lymphotropic virus (HTLV-I)].

Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of 4 HTLV related and 7 HTLV unrelated EOFLs, have been investigated with regard to their immunohistological and clinical features. The HTLV related EOFLs were found to be of the T-cell phenotype and were associated with a poorer prognosis than the HTLV unrelated EOFLs, most of which were of B-cell origin. The comparatively high incidence of T-cell type in our series was considered to be related to the high percentage of HTLV carriers in our district, an area in which adult T-cell leukemia lymphoma has been found to be endemic.

Immunohistochemical study of mononuclear cell infiltrates in squamous cell carcinoma of oral cavity and paranasal sinus.

Serial frozen sections were prepared from 22 squamous cell carcinomas of oral cavity and paranasal sinus. Mononuclear cell infiltrates were stained by the biotin-avidin-horseradish peroxidase method using a panel of 10 mouse monoclonal antibodies to human leukocyte antigens. The degree of infiltration was graded from + + + (marked) to - (absent). The infiltration of anti-Leu-4-reactive cells (Leu-4+ cells) was grade + + or + + + in 14 of 22 cases. In 13 of 22 cases, infiltration of Leu-3a + 3b+ cells (helper/inducer T lymphocytes) was grade + + (moderate). In 5 of 20 cases, infiltration of Leu-2a+ cells (cytotoxic/suppressor T lymphocytes) was grade + +. As for B lymphocytes, infiltration of Leu-12+ cells was grade + + in only 2 of 19 cases. In conclusion, T lymphocyte infiltrates were commonly seen in squamous cell carcinoma in oral cavity and paranasal sinus and the number of patients with grade + + infiltration of helper/inducer T lymphocytes significantly predominated over that of patients with infiltration of cytotoxic/suppressor T lymphocytes grade + +.

Non-Hodgkin's lymphoma of Waldeyer's ring and nasal cavity. Clinical and immunologic aspects.

Twenty-nine cases of non-Hodgkin's lymphoma of Waldeyer's ring (W-NHL) and nasal cavity or paranasal sinus (N-NHL) were studied for tumor-surface marker phenotype and histopathologic correlation with clinical features. Immunostaining procedures on tissue sections by using xenoantisera and monoclonal antibodies to human B- and T-cells enabled the authors to demonstrate precise surface marker phenotypes of tumor cells and, moreover, the histologic localization of normal or neoplastic B- and T-cells in preserving the original structure of lymphoid organs or tumor tissues. In 22 cases of W-NHL, 19 (86%) had B-cell markers and 3 (14%) had T-cell markers, whereas 6 of 7 cases (86%) of N-NHL had T-cell markers. Tumor cells in T-cell lymphomas in W-NHL and N-NHL reacted with antibodies to peripheral T-cells except one case of W-NHL. Rappaport "histiocytic" subtype was heterogeneous with respect to both surface marker characteristics and morphologic features, i.e., seven had B-cell markers and four had T-cell markers, and they were all subdivided into "large cell" or "large cell, immunoblastic" in Working Formulation and "large cell" or "pleomorphic" in Lymphoma Study Group classification. The actuarial survival curve for all T-cell lymphoma patients was characterized by a rapid initial decline and a subsequent plateau, which contained two of the long survivors. In contrast, the B-cell lymphoma group had a more graded decline. The median and actuarial survivals of the T-cell lymphoma group were far inferior to those for the lymphoma group that expressed B-cell markers.

Establishment and characterization of neoplastic cells from a malignant fibrous histiocytoma. A possible stem cell line.

Using the semisolid agar method, neoplastic three clones were isolated from a malignant fibrous histiocytoma. All clones represented morphologically only one type of cells having fine structure similar to that of histiocyte with multiple filopodia. The clones carrying Fc- and C3-surface receptors showed marked immunophagocytosis. They were positive for acid phosphatase, nonspecific esterase, and alpha-1-antitrypsin. These clones were able to display the potential for production of collagenous matrix. Moreover, inoculations of the each clone into nude mice resulted in productions of malignant fibrous histiocytoma with pleomorphic pattern. These tumors were composed morphologically of various types of cells such as immature, histiocyte-like, fibroblast-like, and multinucleated giant cells. These morphologic alterations of histiocytes occurred in all of the three clones in vitro. These findings suggest that the cloned cells established from the malignant fibrous histiocytoma are neoplastic histiocytes with capability to form various types of cells, a possible stem cell.