Aggressive pilomatrixoma of the infra-auricular area: a case report

Although pilomatrixomas are well known among dermatologists and dermatopathologists, head and neck surgeons confronted with these lesions in the infra-auricular region do not consider this benign neoplasm in the differential diagnosis. Aggressive pilomatrixoma is a benign tumor of the hair matrix cells affecting mainly children. Histologically, the border between aggressive pilomatrixoma and pilomatrix carcinoma is still not clear. We report the case of a 15-year-old Turkish boy suffering from an aggressive pilomatrixoma of the infra-auricular region and review the literature about this unclear entity.     

Fluorescent microscopy of hematoporphyrin derivative in the nude mouse tumor model

Mechanisms for localization of hematoporphyrin derivative (HPD) within malignant tissue and for tumor necrosis after photodynamic therapy have not yet been established with certainty. We describe a modified freeze-drying technique to study these mechanisms. Normal tissues and squamous cell carcinoma xenografts were examined in nude mice after administration of HPD. Skin reveals marked fluorescence in connective tissue cells. No fluorescence is visible in surface epithelial cells or keratin. Liver shows diffuse fluorescence only in cells lining sinusoids. In tumor, malignant cells do not fluoresce and connective tissue cells fluoresce brilliantly. This technique provides a clear view of HPD fluorescence, frozen instantaneously in location and time. Fluorescence from connective tissue cells in skin and tumor suggests that localization and photodynamic action may be targeted in part at cells that critically support malignant epithelial cell growth as well as at malignant epithelial cells directly.     

Lymphocyte-Tumor Cell Interaction in Patients with Head and Neck Cancer

Peripheral lymphocytes from 12 patients with squamous cell carcinoma of the head and neck were incubated with autologous tumor explants. Four of the 12 patients demonstrated lymphocyte induced tumor cytotoxicity. These lymphocytes adhered to the tumor cells and deposited a radioactive label from their surface onto tumor cells. The deposition of this label was associated with tumor death. Tissue sections from those patients who demonstrated lymphocyte cytotoxicity showed a marked plasmacytic infiltration. This was in contrast to non-responders where only a desmoplastic tissue response was observed with few inflammatory cells.     

Correlations between histopathological and biological findings in nasopharyngeal carcinoma and its prognostic significance

Forty-five consecutive cases of nasopharyngeal carcinoma were morphologically and immunocytochemically studied using monoclonal (anti-B and anti-T cell) and polyclonal (anti-S100 protein and antilysozyme) antibodies with the peroxidase-anti-peroxidase method to identify infiltrating lymphocytes (T and B cell) and histiocytes (monocytic/macrophagic and dendritic cells) in nasopharyngeal carcinoma. A variable density of dendritic cells was found within the tumor nests in 22 (49%) of 45 nasopharyngeal carcinomas examined; infiltrating macrophages were demonstrated in 15 (33%) specimens and around the tumor in almost all cases. Cases with moderate or marked density of dendritic cells (S100+) survived longer than those without such infiltration (mean 5-year survival rates of 31%, 55%, or 64% in patients with absent, moderate, or marked densities, respectively; P less than 0.05). A significant relationship between monocytic/macrophagic cells (lysozyme+) within the tumor and survival was also found (mean 5-year survival rate of 27% or 61% in patients with absent, moderate, or marked densities, respectively). However, lymphocytic infiltration was not statistically related to a better survival. Analyzing lymphocytic infiltration, we found a large prevalence of T cells in the neoplastic tissue without any prognostic significance. These data were correlated to different histological subtypes according to the principal histological classifications of nasopharyngeal carcinomas (Micheau, et al.; World Health Organization; Cologne University) to individualize the scheme which correlates best with prognosis and biological features of nasopharyngeal carcinomas. Our data suggest that, considering dendritic cells and macrophages within cancer nests, nasopharyngeal carcinoma histiotypes can be correlated to patient prognosis.     

Direct observation of living laryngeal carcinoma cells during invasion of healthy cell formation.

After cloning of laryngeal carcinoma cells from tumor fragments obtained during surgery, the behavior of pure tumor cells was investigated under the inverted microscope. In tissue culture flasks, separately grown tumor cell layers and fibroblast layers were cocultured to visualize the invasion of malignant cells into healthy tissue. Using a time-lapse camera, the cells were recorded. The tumor cells often penetrated the healthy cell formation in a wedge-shaped cell formation. Near the tumor front, an elevated cell motility was found accompanied by continuous changes in the cell shape. Intercellular gaps were broader in the front line than in the more posterior parts of the tumor cell formation. The profound motility of the carcinoma cell enabled selected cells to leave the tumor cell formation completely and to migrate as single cells through healthy tissue. Eventually, some of the single tumor cells migrating through the fibroblast layer moved back to the tumor cell formation. Thus they left healthy appearing tissue behind which was earlier infiltrated by a malignant cell.     

头颈肿瘤组织标本库构建的初步研究

目的 探讨头颈肿瘤组织标本的采集、保存,组织库构建方法,以及信息化管理技术。方法 收集手术切除和活检的头颈肿瘤组织、癌旁组织、远端正常组织及患者和正常人外周血标本(分离出血清、血浆、淋巴细胞、干细胞等),置于液氮或-80℃低温冰箱冷冻保存;同时建立一套系统管理组织标本库,使标本库规模化、信息化、智能化。结果 共收集新鲜组织标本220份,血液标本476份。其中肿瘤组织120份(包括肿瘤组织、癌旁组织);非肿瘤组织100份。肿瘤患者血液标本316份,非肿瘤患者血液标本160份。结论 标本库的建立使少见的头颈肿瘤组织标本集约化、规模化,极大提高了标本利用的效率,达到了资源共享的目的。     

Small cell anaplastic (oat cell) carcinoma of the larynx: report of a case and review of the literature.

The fifth reported patient with primary laryngeal oat cell carcinoma is described. Electron microscopy of tumor cells revealed typical neurosecretory-type granules similar to those described for pulmonary oat cell carcinoma. Analysis of clinical data from all five reported patients revealed that this neoplasm is a virulent one which spreads early and rapidly and kills quickly. Combination chemotherapy and/or radiotherapy, which has significantly prolonged life in patients with oat cell carcinoma of lung, may be indicated as an adjunct to surgery for this rare malignant tumor of the larynx.     

Role of lysosomal cathepsins in naphthazarin- and Fas-induced apoptosis in oral squamous cell carcinoma cells

CONCLUSION: Intracellular cysteine cathepsins are pro-apoptotic factors involved in activation of caspases in two oral squamous cell carcinoma (SCC) cell lines. OBJECTIVE: To study the possible involvement of lysosomal cathepsins in oral SCC cell apoptosis. MATERIAL AND METHODS: Apoptosis was induced in the two human oral SCC cell lines UT-SCC-20A and UT-SCC-24A using naphthazarin or anti-Fas antibodies, and was studied by analysis of caspase activity and nuclear morphology. Involvement of lysosomal cathepsins was investigated using the cysteine cathepsin inhibitor z-FA-FMK and the cathepsin D inhibitor pepstatin A. The amounts of cellular and soluble Fas death receptor were determined by ELISA. RESULTS: Release of cathepsins from the lysosomes to the cytosol was observed early in apoptosis. Cysteine cathepsins were found to be involved in activation of caspases in response to treatment with naphthazarin or anti-Fas antibodies, but inhibition of cysteine cathepsin activity was not sufficient to prevent cell death. Moreover, inhibition of cysteine cathepsin activity resulted in increased expression of the Fas death receptor, suggesting involvement of extracellular cysteine cathepsins in death receptor shedding.     

Cervical metastases of microcystic adnexal carcinoma in an otherwise healthy woman

Microcystic adnexal carcinoma is a rare cutaneous neoplasm characterized by slow but locally aggressive growth, which normally does not lead to systemic metastasis. Frequent local recurrences are reported, which are most likely due to insufficient operative technique. We present the fourth case of cervical ipsilateral metastatic microcystic adnexal carcinoma in an otherwise healthy woman. The patient presented with a previously diagnosed but not completely resected microcystic adnexal carcinoma in the area of the right posterior scalp and two palpable ipsilateral lymph nodes. The tumor was resected using intraoperative snap frozen histological evaluation of the resection borders. In the same procedure two lymph nodes were resected from the right neck. The lymph nodes were histologically assessed and showed infiltration by small strains of tumor cells. After exclusion of a second primary tumor, e.g., mammary carcinoma, as the cause for cervical lymph node metastases, we performed a modified radical neck dissection with resection of the sternocleidomastoid muscle and the accessory nerve, which was histologically proven to be perineurally infiltrated by tumor cells. In this second procedure the histological evaluation of the specimen showed no sign of remaining tumor infiltration. After exclusion of distant metastasis the patient was irradiated with 60 Gy. The patient is well 1 year after the initial treatment without signs of recurrence.     

Langerhans cells in laryngeal carcinoma in relation to prognosis]

Infiltration of Langerhans cells (LCs) was investigated by immunohistochemical methods with the use of anti-S100 protein in 25 cases of stage II and 50 cases of stage III laryngeal carcinoma. Varying population densities of S100 positive LCs were noted. LCs were mainly interspersed among the tumor cells. The prognosis of patients with stage II and stage III laryngeal carcinoma correlated well to the density of LCs in tumor tissue in patients with a marked infiltration of LCs, survival time was longer than in those cases with only a slight infiltration (P < 0.05). This indicates that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor in laryngeal carcinoma.     

Role of lysosomal cathepsins in naphthazarin- and Fas-induced apoptosis in oral squamous cell carcinoma cells

Conclusion. Intracellular cysteine cathepsins are pro-apoptotic factors involved in activation of caspases in two oral squamous cell carcinoma (SCC) cell lines. Objective. To study the possible involvement of lysosomal cathepsins in oral SCC cell apoptosis. Material and methods. Apoptosis was induced in the two human oral SCC cell lines UT-SCC-20A and UT-SCC-24A using naphthazarin or anti-Fas antibodies, and was studied by analysis of caspase activity and nuclear morphology. Involvement of lysosomal cathepsins was investigated using the cysteine cathepsin inhibitor z-FA-FMK and the cathepsin D inhibitor pepstatin A. The amounts of cellular and soluble Fas death receptor were determined by ELISA. Results. Release of cathepsins from the lysosomes to the cytosol was observed early in apoptosis. Cysteine cathepsins were found to be involved in activation of caspases in response to treatment with naphthazarin or anti-Fas antibodies, but inhibition of cysteine cathepsin activity was not sufficient to prevent cell death. Moreover, inhibition of cysteine cathepsin activity resulted in increased expression of the Fas death receptor, suggesting involvement of extracellular cysteine cathepsins in death receptor shedding.     

Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck produces a prostaglandin, PGE2, a potent inhibitor of cellular immune responses. We tested the effects of prostaglandin synthetase inhibition on the infiltration of squamous cell carcinoma of the head and neck with host lymphocytes. Tumor tissue samples were obtained from six patients (age range, 51 to 72 years) who presented with squamous cell carcinoma of the head and neck before and after 14 days of treatment with indomethacin (50 mg administered orally three times a day). Tumor-infiltrating immune cells were assayed in frozen tissue samples by indirect immunofluorescence. An eightfold increase in CD2+ lymphocytes compared with pretreatment tissue was observed. The number of CD4 and CD8 lymphocytes increased similarly. CD57 lymphocytes increased 15-fold and CD11b cells increased 11-fold. No infiltrating B-cell populations were evident. Double-labeling studies revealed that the mononuclear cells were located outside blood vessel walls, indicating that they had infiltrated the tumor parenchyma. Our findings demonstrate that the administration of indomethacin is associated with the increased immune cell infiltration of squamous cell carcinoma of the head and neck. This suggests that inhibition of PGE2 synthesis as it occurs in the tumor and or systemically may contribute to the homing of mononuclear cells to the tumor. These data suggest a mechanism to account for the clinical response to indomethacin previously reported in squamous cell carcinoma.     

Langerhans cell related inflammatory reaction in laryngeal squamous cell carcinoma

The major cells involved in cancer cell kill are the T lymphocytes. However, T cells need to be activated upon antigen presentation, which is mediated by the antigen presenting cells, one of which is the Langerhans cell (LC). The purpose of this study was to assess the significance of LC and inflammatory cell infiltration in the laryngeal squamous cell carcinoma (LSCC). Forty-five patients who were operated on for LSCC between 1992 and 1999 were included in the study. The clinical and histopathological features of the patients were reviewed. A semiquantitative estimation of the lymphocyte dominant inflammatory reaction within and around the tumor was performed. Anti S-100 antibodies were used for immunohistochemical detection of LCs. Horseradish peroxidase method was used. LCs were present in almost all of the specimens within and around the tumor tissue. The S-100 results did not associate with grade, T and N stages, tumor stage, laryngeal site of involvement and survival (P>0.05). The S-100 results significantly associated with inflammatory reaction in the tumor tissue (P<0.01). In conclusion, the LC related response is not important to inhibit regional metastasis by cancer cells. The LC is not a reliable tool to determine prognosis of the patients with LSCC in the clinical practice.     

Nonsquamous neoplasms of the larynx

While squamous cell carcinoma is the most common neoplasm to involve the larynx, several other histologic tumor types can occur. The laryngologist should consider a nonsquamous neoplasm when the tumor is long-standing, pigmented, covered by intact mucosa, or there is a history of neoplasia. Careful endoscopy, often using microlaryngoscopy, and careful handling of the tissue will ensure accurate diagnosis.     

RECK和MMP-2在下咽癌中的表达及相关性研究

目的 探讨RECK与MMP-2蛋白表达与下咽癌侵润和转移的关系.方法 应用手术方法取下咽癌原发灶、癌旁组织及淋巴节转移组织22例,另取良性病变(声带息肉)10例作为对照,应用免疫组化检测RECK、MMP-2蛋白表达,并与下咽癌不同临床分期进行相关性分析.结果 RECK的表达水平在下咽癌原发灶、转移灶中均明显低于癌旁组...     

Experimental studies on specific immunotherapy in nasopharyngeal carcinoma (NPC)

Summary The IgG fraction was isolated from the serum of patients with nasopharyngeal carcinoma and conjugated with ferritin or horseradish peroxidase. The conjugate was injected i.v. in nude mice on which transplanted nasopharyngeal carcinomas were growing. Electron-microscopic examination of the tissue revealed localization of the antibodies of the IgG class (VCA, EBNA) exclusively within the tumor cell association of NPC transplants, mainly on the outer cell membrane, on mitochondria of the cytoplasm, and on the membranes of the endoplasmic reticulum. The possibility of conjugating such EBV-specific and thus NPC tumor cell-related antibodies with cytostatically active substances so as to convey the cytostatics directly to the tumor cells is discussed.Supported by the Deutsche Forschungsgemeinschaft     

Study on ceramide expression and DNA content in patients with healthy mucosa, leukoplakia, and carcinoma of the larynx

OBJECTIVE: To investigate the expression of ceramide produced by sphingomyelin and DNA content in patients with healthy laryngeal mucosa, leukoplakia, and laryngeal carcinoma. DESIGN: A retrospective review of the clinical and surgical records of 178 patients with leukoplakia of the larynx; 23 of them developed laryngeal carcinoma. SETTING: University medical center. PATIENTS: One hundred seventy-eight consecutive patients with leukoplakia of the larynx were identified from the archived pathology files of the Eye Ear Nose and Throat Hospital of Fudan University from January 1, 1990, to December 30, 2001. Among them, 23 developed laryngeal carcinoma. Flow cytometry and immunohistochemistry were performed to test DNA content and ceramide expression in healthy tissue, tissue with leukoplakia, and tissue with laryngeal carcinoma from the same patient. RESULTS: Among 23 patients with leukoplakia, 20 had aneuploidy and 3 had diploidy. The healthy tissues were all diploids, and the tissues with laryngeal carcinoma were all aneuploids. The expression of ceramide decreased gradually from healthy tissue to tissue with leukoplakia to tissue with laryngeal carcinoma (0, no staining; 1+, weak staining; 2+, mild staining; 3+, moderate staining; 4+, strong staining; and 5+, the highest staining intensity). The expression of ceramide in DNA diploid cells is stronger than in aneuploid cells. CONCLUSIONS: Ceramide, the second messenger in apoptosis, may associate with the progress of leukoplakia to carcinoma of the larynx. The reduction of ceramide may contribute to laryngeal carcinogenesis.     

Hurthle cell neoplasms of the thyroid

OBJECTIVES/HYPOTHESIS: Hurthle cell tumors are a variant of follicular cell neoplasms. The purpose of the study was to determine the reliability of intraoperative frozen-section analysis for diagnosing Hurthle cell carcinoma and Hurthle cell neoplasm and to evaluate age, gender, and tumor size differences in the incidence of Hurthle cell carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: The records of all patients undergoing thyroid surgery at Long Island Jewish Medical Center (Long Island Campus of the Albert Einstein College of Medicine, New Hyde Park, NY) from 1990 to 2000 were reviewed. Patients were identified whose final pathological finding was Hurthle cell neoplasm or Hurthle cell carcinoma. Age at diagnosis, gender, tumor size, and correlation between frozen-section analysis and final pathological finding was determined. RESULTS: One hundred sixteen patients had Hurthle cell tumors on final pathological finding (49 had Hurthle cell carcinoma and 67 had Hurthle cell neoplasm). Eleven of these patients had incidental papillary carcinoma. There were 24 men and 92 women. Sixty-seven percent of the men (16 of 24) and 36% of the women (33 of 92) had Hurthle cell carcinoma on final pathological finding. The mean ages for Hurthle cell neoplasm and Hurthle cell carcinoma groups were 53 (median age, 50 y) and 58 years (median age, 61 y), respectively. One hundred eleven patients had intraoperative frozen-section analysis. Of the 49 patients with Hurthle cell carcinoma, 9 (19%) were diagnosed by frozen-section analysis, 36 (75%) had indeterminate frozen-section analysis, 3 (6%) were discovered to have papillary carcinoma on frozen-section analysis, and 1 did not have a frozen-section analysis. Multivariate analysis indicated that size correlated with malignancy and that gender did not (P =.0015). CONCLUSIONS: In the study population, only 19% of patients were discovered to have Hurthle cell carcinoma on frozen-section analysis. Sixty-seven percent of men with Hurthle cell neoplasm had malignancies, compared with 36% of women, and this difference was statistically significant.     

Human medullary thyroid carcinoma. Initial characterization and in vitro differentiation of two new cell lines

Medullary carcinoma of the thyroid (MCT), a tumor of calcitonin (CT)-secreting C cells, can display a variable malignant potential with poor prognosis linked to decreased cell differentiation. In vitro study of MCT has been hampered by the fact that few cell lines derived from this neoplasm have been available for study. Herein are reported the characteristics of two new lines derived from human MCT that are tumorigenic in athymic mice and do not secrete CT. After treatment with various concentrations of retinoic acid (a vitamin A derivative) and cyclic adenosine monophosphate, both lines exhibit the traits of more differentiated cells with a decrease in cellular proliferation and an increase in cytoplasmic CT content as shown by in situ immunoperoxidase staining. These cell lines should prove of great value in the study of the biology of MCT and the mechanisms underlying induced differentiation in this type of tumor.     

Soluble Adhesion Molecules and Cytokines in Tumor-associated Tissue Eosinophilia of Nasopharyngeal Carcinoma

The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils breaking through the vascular wall and pervading the tumor stroma. The margination and trans-endothelial migration of eosinophils in a typical inflammatory reaction depend on the activating effects of certain cytokines and the expression of adhesion molecules on the eosinophils and endothelial cells. In order to investigate whether the adhesion molecules and activating cytokines play a role in eosinophil tumor infiltration, we measured the serum levels of 3 adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and 40 normal healthy subjects. We found that the NPC patients had higher serum levels of all three soluble adhesion molecules than the normal subjects but the levels of adhesion molecules failed to correlate with the TATE phenomenon. The levels of IL-3 and IL-5 appeared not to differ between the NPC and control groups. We postulate that the three soluble adhesion molecules do not play a major role in TATE and that their elevation in serum may be due to local and/or systemic immune responses.