Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare, highly aggressive neoplasm that primarily affects the major salivary glands. It is a distinct clinicopathological entity characterized by its morphologic resemblance to ductal carcinoma of the breast, a high incidence of regional lymph node metastasis, and distant dissemination. Frequent expression of androgen receptor (AR) but not estrogen receptor or progesterone receptor in SDCs suggests that SDC bears a close immunophenotypic homology with prostatic carcinoma. An AR-mediated autocrine growth pathway consisting of epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), has been implicated in the carcinogenesis of prostatic carcinoma. Androgens, in the presence of AR, mediate their mitogenic effects on prostatic cancer cells by up-regulating the transcriptional and translational activities of EGFR and TGF-alpha. Through an autocrine mode of action, TGF-alpha produced in the tumor cells binds to its receptor, EGFR, which is also expressed by these cells, resulting in a proliferative response. OBJECTIVE: To investigate whether a TGF-alpha/EGFR autocrine pathway is present in SDCs. DESIGN: Retrospective analysis of the expression of AR, EGFR, and TGF-alpha in 12 SDCs. SETTING: An academic medical center. RESULTS: Salivary duct carcinoma expresses AR, TGF-alpha, and EGFR in 11 (92%), 8 (67%), and 11 (92%) of 12 cases, respectively. CONCLUSION: An AR-mediated TGF-alpha/EGFR autocrine pathway may be implicated in the tumorigenesis of SDC.

Selective neck dissection in the management of the clinically node-negative neck.

OBJECTIVE: To evaluate the efficacy of the selective neck dissection (SND) in the management of the clinically node-negative neck. STUDY DESIGN: Case histories were evaluated retrospectively. METHODS: The results of 300 neck dissections performed on 210 patients were studied. RESULTS: The primary sites were oral cavity (91), oropharynx (30), hypopharynx (16), and larynx (73). Seventy-one necks (23%) were node positive on pathological examination. The number of positive nodes varied from 1 to 9 per side. Of necks with positive nodes, 17 (24%) had extracapsular spread. The median follow-up was 41 months. Recurrent disease developed in the dissected neck of 11 patients (4%). Two recurrences developed outside the dissected field. The incidence of regional recurrences was similar in patients in whom nodes were negative on histological examination (3%) when compared with patients with positive nodes without extracapsular spread (4%). In contrast, regional recurrence developed in 18% of necks with extracapsular spread. This observation was statistically significant. Patients having more than two metastatic lymph nodes had a higher incidence of recurrent disease than the patients with carcinoma limited to one or two nodes. Recurrence rate in the pathologically node positive (pN+) necks was comparable to recurrence in those pathologically node negative (pNO) necks in the patients who did not have irradiation. CONCLUSION: SND is effective for controlling neck disease and serves to detect patients who require adjuvant therapy.

Prognostic value of p53, proliferating cell nuclear antigen, and Ki-67 expression in undifferentiated nasopharyngeal carcinomas.

In this study the prognostic importance of p53, proliferating cell nuclear antigen (PCNA), and Ki-67 expression was analyzed along with the clinical parameters in 35 consecutive patients with undifferentiated nasopharyngeal carcinomas. Immunohistochemistry was used to detect p53, PCNA, and Ki-67 staining. Among the clinical findings, stage IV disease (P = 0.01), cranial nerve paralysis (P = 0.02), and lymph node metastasis (P = 0.06) were associated with shorter survival. The p53 positivity correlated with the presence of lymph nodes, but it was not a significant factor to predict the outcome. PCNA expression was not found to be a prognostic indicator. On the other hand, the proliferative value of Ki-67 staining was suggestive of prognosis. A proliferation index of Ki-67 less than 10% indicated longer survival (P = 0.03). There was no correlation between Ki-67 staining and PCNA index. As a result, the prognostic value of Ki-67 may alert the physician to more aggressive and adjuvant treatment modalities.

Comparison of regional recurrence rates of radical and comprehensive neck dissection type 3 in N0 laryngeal cancer.

To determine whether comprehensive neck dissection (CND) type 3 could accomplish regional tumor control as well as radical neck dissection (RND) in clinically N0 laryngeal cancer patients, we compared the regional recurrence rates of 316 N0 laryngeal cancer patients. In the 316 N0 patients, 486 neck dissections were performed. For 170 patients the dissection was bilateral, and for 146 patients it was unilateral. Of these, 193 were type 3 CNDs, and 293 were RNDs. In 30 (15.5%) of 193 type 3 CNDs and in 53 (18.1%) of 293 RNDs, metastatic lymph nodes were determined histopathologically in neck dissection specimens. The difference in cervical lymph node metastasis rates was not statistically significant (P > 0.05). During follow-up, 3 patients who underwent CND type 3 (1.6%) and 12 who underwent RND (4.1%) had regional recurrences. The difference between recurrence rates was not statistically significant (P > 0. 05). A conclusion was reached that CND type 3 safely provided regional cancer control in N0 laryngeal cancer and that it might be performed to decrease the morbidity of RND.

Prognostic value of p53 expression and histopathological parameters in squamous cell carcinoma of oral tongue.

The TNM staging system is helpful but not enough to determine prognosis of the patients with squamous cell carcinoma of the oral tongue. T-stage alone is not suggestive for prediction of occult nodal metastases. For this reason, histopathological examination of 70 patients with squamous cell carcinoma of the oral tongue was done retrospectively. The histological differentiation, tumour thickness, perineural and lymphovascular space invasions, the amount of lymphocyte infiltration and pattern of tumour invasion were examined. Immunohistochemical examination was used to determine p53 immunoreactivity as well. The effect of these histopathological parameters and p53 immunoreactivity on nodal metastases and locoregional recurrence were analyzed using the chi-squared test. In terms of nodal metastases the only statistically significant difference between the two groups was tumour thickness, either < 9 mm or > 9 mm (p < 0.05, chi 2 = 17.182). Tumour thickness, perineural invasion, lymphovascular space invasion, the amount of lymphocyte infiltration all correlated statistically with locoregional recurrence (p < 0.05, chi 2 = 6.293 for tumour thickness; p < 0.06, p = 0.054 for perineural invasion; p < 0.05, chi 2 = 8.689 for lymphovascular space invasion; p < 0.05, chi 2 = 5.320 for lymphocyte infiltration). The immunoreactivity of p53 correlated significantly with larger primary tumour size (p < 0.05, chi 2 = 5.440, lymph node metastases (p < 0.05, chi 2 = 4.093) and with pathological tumour stage (p < 0.05, chi 2 = 5.713). These results reveal that the above-mentioned histological parameters and p53 determination could be used for handling a specimen from an anterior tongue squamous cell carcinoma.

Myositis ossificans in the neck.

Myositis ossificans is a non-neoplastic heterotopic bone formation within muscle or soft tissues. The most commonly involved muscles are the muscles of the upper arm and thigh. Occurrence in the head and neck is rarely encountered clinically. A 53-year-old Turkish man (farmer) was operated on for traumatic myositis ossificans circumscripta in his neck. During the operation the mass was found to originate from the scalenus medius muscle and was readily and completely dissected from surrounding tissues. The histologic examination of the specimen revealed focal cartilage and mature bone tissue, which was compatible with the late stage of myositis ossificans. In 5 years of follow-up, the patient has remained asymptomatic and no signs of recurrence have been noted.

Prognostic significance of histopathological parameters in cancer of the larynx.

In this study we investigated the prognostic significance of differentiation, the mode of tumor invasion to surrounding tissues, the microscopic appearance of tumor, peritumoral lymphocytic infiltration and cartilage involvement according to disease-free survival, and the recurrence and presence of cervical lymph node metastasis in cancer of the larynx. Only the mode of tumor invasion to surrounding tissues was significantly related to survival (P < 0.05). The patients with "well-defined margin" tumors survive significantly longer than those with "groups of cells, no distinct margin." Patients with supraglottic tumors and a mode of invasion other than "well-defined margin" have a significantly higher risk of recurrence (P < 0.05) and therefore require adjuvant therapy. Patients with poorly differentiated, cartilage invading, ulcerative supraglottic tumors, and patients with glottic tumors having diffusely infiltrating margins, certainly need elective neck dissection (P < 0.05). According to the multivariant analysis, none of the factors significantly affect disease-free survival independently (P > 0.15). According to multiple logistic regression and cox regression analysis, in decreasing order of significance, the mode of invasion, microscopic tumor appearance and lymphocytic infiltration significantly affect the recurrence and time between surgery and the development of recurrence independently (P < 0.15).

Hamartoma of the larynx: a case of unusual bleeding after microlaryngoscopy.

We report on a rare complication of surgery in a 36-year-old man who had undergone removal of a hamartoma of the larynx. The patient had developed a submucosal lesion in the left ventricular fold, which was removed by surgical microlaryngoscopy. Following the excision, the patient began to experience an excessive amount of bleeding at the surgical site. Before hemostasis was achieved, the patient had lost almost 1,000 ml of blood. Although the occurrence of hemorrhage during surgical laryngoscopy is rare, surgeons should be aware of and prepared for this possibility.

Prognostic significance of PCNA expression in laryngeal cancer.

OBJECTIVE: To assess the prognostic value of proliferating cell nuclear antigen (PCNA) in laryngeal carcinoma and its relation with other known prognostic clinicopathologic variables. DESIGN: A retrospective cohort study of 92 patients chosen randomly from patients treated between 1964 and 1993 with the diagnosis of laryngeal cancer. Prognostic factors including PCNA expression, grade, lymphovascular invasion, depth of tumor margins, neck metastasis, and clinical outcome were evaluated. SETTING: Hacettepe University Medical Faculty, Ankara, Turkey. PATIENTS: Eighty-five men and 7 women operated on for squamous cell carcinoma of the larynx were studied. Sixty-nine patients had total and 20 patients had partial laryngectomy with neck dissection, and 3 patients had endolaryngeal tumor excision. INTERVENTION: Hematoxylin and eosin-stained sections were reevaluated for grade, lymphovascular invasion, and depth of tumor margins; sections stained with monoclonal antibody against PC10 were examined for PCNA expression. RESULTS: The PCNA index correlated with grade, lymphovascular invasion, depth of tumor margins, neck metastasis, and local-regional recurrence. The PCNA index values of patients with occult metastasis were significantly higher than those of patients without metastasis (P=.006). CONCLUSIONS: The PCNA index is a more sensitive variable than grade in predicting tumor proliferation, occult lymph node metastasis, and prognosis. These results suggest that the PCNA index can be used in decision making for treatment and assessment of prognosis in laryngeal carcinomas.

Possible prognostic value of histopathologic parameters in patients with carcinoma of the oral tongue.

The current TNM staging system is helpful but still not enough to accurately determine prognosis of the patients with squamous cell carcinomas of the oral tongue. Histopathologic variables, however, may be more helpful for predicting nodal metastasis and locoregional recurrences. In this respect, histopathologic examinations were done retrospectively of tumor specimens from 60 patients with squamous cell carcinomas of the oral tongue. Besides T-stage and nodal involvement, histopathologic parameters of tumor thickness, perineural invasion, lymphovascular space invasion, the extent of lymphocyte infiltration and the invasion pattern statistically correlated with locoregional recurrences. For nodal metastasis, tumor thickness of 10 mm or more and the type of invasion pattern were statistically significant. These results revealed that the variables described should be used for managing oral tongue cancers.

Prognostic significance of vascular and perineural invasion in cancer of the larynx.

PURPOSE: Perineural and vascular invasion are generally recognized as poor prognostic factors in cancer. The authors report the prognostic significance of perineural and vascular invasion in cancer of the larynx. MATERIALS AND METHODS: The laryngectomy specimens of 94 patients with squamous cell carcinoma of the larynx were analyzed histopathologically for vascular and perineural invasion. Prognostic significance of vascular and perineural invasion was evaluated related to the cervical lymph node metastasis, recurrence, and disease-free survival. RESULTS: Vascular invasion significantly influences cervical lymph node metastasis for supraglottic tumors, yet not for glottic and transglottic tumors. Perineural invasion has marginal significance in cases of cervical lymph node metastasis of supraglottic tumors; it has no significance in cases of cervical lymph node metastasis of glottic and transglottic tumors. Vascular invasion significantly increases local and regional recurrence rate, but not distant metastasis rate. Perineural invasion significantly increases local recurrence rate, but not regional recurrence and distant metastasis rate. The disease-free survival is significantly shortened by the presence of vascular and perineural invasion. According to multivariant analysis, neither vascular nor perineural invasion significantly effects the disease-free survival independently (P> .15). The presence of vascular invasion significantly affects the recurrence independently (P=.045). The presence of vascular invasion significantly reduces the interval between surgery and the development of recurrence (P=.013). CONCLUSION: The presence of vascular and perineural invasion should be checked in every laryngectomy specimen because both have a significant prognostic value; both influence the disease-free survival and recurrence significantly. Vascular invasion significantly increase cervical lymph node metastasis of supraglottic tumors; perineural invasion has only marginally significant effect on cervical lymph node metastasis of supraglottic cancers. Vascular invasion plays an independent role in determining the recurrence.

nm23 Protein expression in larynx cancer and the relationship with metastasis.

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene and has been demonstrated to correlate inversely with metastatic potential in several tumours. To elucidate the role of nm23 in larynx carcinomas, we examined using immunohistochemistry the expression of the nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23 Protein was expressed in all the carcinomas as well as in non-neoplastic larynx mucosa. Overexpression of nm23 protein was found in the majority of primary tumours compared with corresponding normal mucosa, while decreased expression was associated with poor differentiation and distant metastasis and/or recurrence. No significant difference in age, sex and stage was found between primary tumours with high and low nm23 protein expression. These results suggest that decreased nm23 protein expression may play a role in metastasis and/or recurrence in larynx cancer and therefore could be used as a prognostic factor.

Ataxia telangiectasia and mucoepidermoid carcinoma of the parotid gland: a case report.

Ataxia telangiectasia (AT) is an immunodeficiency disorder with increased incidence of malignancy. Most of the tumors are lymphomas, and salivary gland neoplasms are very uncommon. A case with ataxia telangiectasia and mucoepidermoid carcinoma of the parotid gland, the second case in English literature, was presented. The treatment was discussed under the view of the literature.