Clinical and pathologic characterization of mucosa-associated lymphoid tissue lymphoma of the head and neck.

Mucosa-associated lymphoid tissue (MALT) has recently been recognized as a possible site of origin for low-grade lymphomas of the B-cell type. Though relatively rare, these MALT lymphomas may arise within several sites in the head and neck, and often present diagnostic and therapeutic challenges. We review 4 cases of primary MALT lymphoma of the head and neck, treated with surgical excision (3 cases), irradiation (2 cases), and chemotherapy (1 case), to further characterize this new subtype of head and neck malignancy. The mean time from onset of symptoms to histologic diagnosis was 15 months. Fine needle aspiration identified an atypical lymphoid infiltrate in only 1 of 3 patients. Immunohistochemical analysis was essential in establishing the diagnosis of MALT lymphoma in all 4 of the cases, and demonstrated characteristic negative staining for CD3, CD5, and CD43, positive staining for CD20, and monotypic staining for either kappa or lambda light chain immunoglobulin markers. All patients achieved complete remission after primary therapy, and all remain free of disease with follow-up ranging from 6 to 54 months (mean 33 months). The diagnosis of MALT lymphoma should be considered in cases of atypical lymphoid infiltrates in the head and neck, and increased awareness coupled with detailed immunohistochemical analysis is essential to securing an accurate diagnosis. Clinical remission of MALT lymphoma may be achieved with several modalities, but further study will be required to determine the long-term response to treatment.

Postoperative radiation of free jejunal autografts in patients with advanced cancer of the head and neck.

BACKGROUND: Free jejunal autografts increasingly are being used to repair the pharynx after resections of head and neck carcinomas. Doses of greater than 45 Gy are generally considered to be above the tolerance of the small bowel, whereas the dose range for effective postoperative radiotherapy of advanced head and neck cancers is between 57.6 Gy and 63 Gy. Between July 1988, and December, 1992, 29 patients at the M. D. Anderson Cancer Center were treated with a combination of resection of the advanced head and neck cancer, reconstruction with free jejunal autograft, and postoperative radiation. Planned reductions in postoperative doses due to the presence of the jejunum within the field were not made. This retrospective study analyzes the outcome of these patients with attention to survival, local-regional control, and complications. METHODS: Twenty-seven of the 29 study patients had squamous cell carcinoma of the larynx or pharynx; 24 of these patients had Stage III or Stage IV disease. Two patients had recurrent papillary thyroid carcinoma. The median number of days from surgery to the start of radiation was 34. Radiation doses to the tumor bed ranged from 50 Gy to 72 Gy. The median doses to the tumor bed and the jejunal autograft were both 63 Gy. Surviving patients were followed from 12 to 68 months (median, 20 months) from the time of their surgery. RESULTS: The actuarial 2-year survival rate was 51%. Nine patients had local or regional recurrences above the clavicles. The 2-year local-regional control and freedom from relapse rates were 71 and 50%, respectively. The most severe complication during radiation was confluent mucositis in greater than 50% of the treated area, which developed in two patients. No patient developed a late complication related to the jejunal autograft. CONCLUSIONS: Postoperative radiation to free jejunal autografts used for pharyngeal reconstruction can be delivered safely. Doses in this setting of 57.6 Gy to 63 Gy depending on the anticipated risk of recurrence based on clinical, surgical, and pathologic findings are recommended. The presence of a free jejunal autograft did not require a reduction of the desired doses used for patients with postoperatively irradiated head and neck cancer.

Laryngeal preservation for advanced laryngeal and hypopharyngeal cancers.

OBJECTIVE: To compare a single institutional experience with combination chemotherapy and radiation for laryngeal preservation with historical age-, sex-, stage-, and site-matched controls who underwent laryngectomy for cancer of the larynx or hypopharynx. DESIGN: Fifty-five patients with stage III or IV laryngeal and hypopharyngeal squamous carcinoma were prospectively entered into a protocol to receive three cycles of cisplatin (+/- bleomycin sulfate) and fluorouracil and radiation therapy from 1986 to 1991 (group 1). Following two cycles of chemotherapy, the clinical tumor response was assessed and responders received a third cycle of chemotherapy followed by definitive radiation therapy. Nonresponders underwent surgical salvage. Two patients in the surgical control group were matched to each protocol patient (n = 110, group 2) regarding site, stage, sex, and age (+/- 7 years) without knowledge of patient outcome. SETTING: A tertiary cancer referral center, The University of Texas M. D. Anderson Cancer Center, Houston. RESULTS: Following chemotherapy, the tumor response rate for group 1 was complete in 38% and partial in 31%. With a median follow-up of 24 months (group 1) and 37 months (group 2), the Kaplan-Meier 2-year disease-specific survival for group 1 and 2 was 63% and 74%, respectively (P = .251). Among group 1 patients, 67% retained their larynges. Local recurrences were more frequent among the laryngeal preservation group (P = .001), whereas distant metastasis was more frequent among controls (P = .35). Thirty-three percent (18/55) of group 1 patients required total laryngectomy. Examining these subsets of patients showed that of the 67% (n = 37) of patients who retained their larynges, their 2-year survival was 56%, not significantly different from their respective controls (n = 74), 71%. Additionally, 2-year survival among the 18 group 1 patients who required salvage laryngectomy was 75% as compared with 80% for their matched controls (n = 36). CONCLUSIONS: These results document the results of chemotherapy and radiation therapy in the treatment of patients with advanced laryngeal and hypopharyngeal cancers in preserving the larynx. Although local control is significantly compromised among these patients, there is no compromise in overall survival when combined with prompt surgical salvage.

Postoperative radiotherapy for cutaneous melanoma of the head and neck region.

PURPOSE: To assess the efficacy and toxicity of elective-adjunctive radiotherapy given in five 6-Gy fractions to patients with cutaneous melanoma of the head and neck at high risk for local-regional relapse. METHODS AND MATERIALS: From 1983 to August 1992, 174 patients (132 men and 42 women) were enrolled. The ages ranged from 16 to 89 years (median: 54 years). One group (n = 79) received elective irradiation after wide local excision of lesions > or = 1.5 mm thick, or Clark's level IV-V, a second group (n = 32) received adjunctive irradiation after excision of primary lesions plus limited neck dissection, and a third group (n = 63) received irradiation after neck dissection for nodal relapse. Each group had a projected local-regional recurrence rate of approximately 50%. The radiotherapy consisted of five fractions of 6 Gy each, specified at Dmax, delivered twice a week, to a total dose of 30 Gy in 2.5 weeks. Electron beams of appropriate energies were used whenever possible. Junction lines between adjoining fields were moved twice to minimize dose heterogeneity. Patients were seen at regular intervals to assess disease status and therapy-related complications. Patients who relapsed were treated as indicated by the clinical status. RESULTS: With a median follow-up of 35 months, 111 of 174 patients were alive. The disease recurred above the clavicles only in six patients, at distant sites in 58 patients, and both local-regionally and at distant sites in nine patients. The actuarial 5-year local-regional control (LRC) and survival rates for the whole group were 88% and 47%, respectively. The thickness of the primary lesion, presence of more than three positive nodes, and extracapsular extension did not influence the LRC rate after radiotherapy (range: 85-92%). However, lesion thickness strongly affected the 5-year survival rate of group 1 patients (i.e., 100% for < or = 1.5 mm thick, but Clark's level IV, 72% for > 1.5-4 mm, and 30% for > 4 mm). In groups 2 and 3, the 5-year survival rate of patients with > three involved nodes was lower than that of patients with one to three positive nodes (23% vs. 39%). The acute tolerance to adjunctive radiotherapy was excellent. Late radiation complications were observed in only three patients. These were moderate neck fibrosis, mild ipsilateral hearing impairment, and transient exposure of external auditory canal cartilage. CONCLUSION: The safety of this hypofractionated radiotherapy regimen in the management of cutaneous melanoma was established in this study. The overall 5-year actuarial LRC rate of 88% was much higher than that of our historical group and that reported in the literature (50%). The survival rate of patients with lesion of 1.5-4 mm thickness was also higher than that observed in other series. Based on these results a prospective randomized study to further define the role of adjunctive postoperative radiotherapy is planned.

High correlation with survival of proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of the parotid gland.

We tested the hypothesis that proliferating cell nuclear antigen can predict survival in patients with mucoepidermoid carcinoma. Formalin-fixed, paraffin-embedded, tissue resected specimens from 43 patients with no prior treatment for mucoepidermoid carcinoma of the parotid gland were immunostained with the PC10 monoclonal antibody to proliferating cell nuclear antigen with the peroxidase/antiperoxidase method. Proliferating cell nuclear antigen levels were defined as the number of nuclei with strong immunostaining divided by the total cell count and were expressed as percentages. Both univariate and multivariate analyses were performed on 12 additional prognostic variables to determine the relative proliferating cell nuclear antigen level to predict survival. The median proliferating cell nuclear antigen level was 7. Five percent of patients with proliferating cell nuclear antigen levels less than 7 died of their disease compared with 48% of those with proliferating cell nuclear antigen levels of 7 or more. Multivariate analysis indicates proliferating cell nuclear antigen to be the most important parameter in predicting survival. Thus the measurement of proliferating cell nuclear antigen is a useful predictor of survival for patients with mucoepidermoid carcinoma of the parotid gland.

Phase I/II study of cisplatin, 5-fluorouracil and alpha-interferon for recurrent carcinoma of the head and neck.

Current chemotherapy regimens have failed to demonstrate a significant impact on the overall survival of patients with recurrent head and neck cancer; therefore, new agents or combinations of agents are necessary to improve outcome. Alpha-interferon potentiates the activity in vitro of both agents of one of the most active regimens currently available, cisplatin and 5-fluorouracil. The purpose of the current study was to evaluate the feasibility and efficacy in patients with recurrent head and neck cancer of adding alpha-interferon to cisplatin 14 mg/m2 daily and 5-fluorouracil 700 mg/m2 daily for 5 days. No significant toxicity occurred with alpha-interferon at dose level 0, 1 x 10(6) units/m2 daily for five days. Of four patients treated at dose level +1, alpha-interferon 3 x 10(6) units/m2, two developed prolonged grade III neutropenic following the fourth course. One of three patients developed grade IV thrombocytopenia and 6 of 13 courses at this dose level resulted in grade III neutropenia. A phase II study was performed in 19 patients with cisplatin 17 mg/m2/day, 5-fluoruracil 700 mg/m2/day and alpha-interferon 3 x 10(6) units/m2/day. During the phase II study grade III neutropenia occurred in 6 patients and grade IV neutropenia in another patient during at least one course. Grade III and IV thrombocytopenia occurred in one patient each during the phase II study. Overall, major responses occurred in 7 or 23 patients (30%): 5 in phase I and 2 in phase II. In conclusion, the addition of alpha-interferon to cisplatin and 5-fluorouracil is feasible, but does not appear to increase response rates in recurrent head and neck cancer.

Carcinomas of the lacrimal drainage system.

Primary carcinomas of the lacrimal drainage system are rare. These malignant neoplasms typically present as noncompressible, nontender masses with low-grade dacyrocystitis and/or unilateral epiphora. Lymph node metastasis may occur late in the disease course. Complete surgical resection is the best treatment choice; extensive procedures such as orbital exenteration and maxillectomy may be necessary for complete tumor extirpation. Further adjunctive radiotherapy may improve local control. We present two cases of carcinoma of the lacrimal drainage system, including one locally controlled tumor with apparent lymph node metastasis that occurred 21 years after primary treatment. A review of the histopathology and literature concerning carcinomas of the lacrimal drainage system is presented.

Predicting occult lymph node metastasis in parotid cancer.

To determine the factors predictive of occult cervical metastases, we retrospectively reviewed the charts of 99 previously untreated patients with a primary parotid malignancy who underwent elective neck dissection between 1960 and 1985. Univariate and multivariate analyses were performed to determine the predictive value of 11 factors. The univariate study found facial nerve paralysis, extraparotid extension, and perilymphatic invasion statistically significant. In the multivariate analysis of preoperative factors, facial nerve paralysis was most predictive of occult disease. If the variable pool was expanded to include a fine-needle biopsy, tumor grade became the most important preoperative variable. When the analysis was further expanded to include a parotidectomy, the most influential factors were patient age, perilymphatic invasion, and extraparotid tumor extension. This report identifies the variables predictive of occult neck disease in parotid cancer.

Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial.

PURPOSE: This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors. METHODS AND MATERIALS: Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving > 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk. RESULTS: The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of < or = 54 Gy had a significantly higher primary failure rate than those receiving > or = 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at > or = 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, > or = 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status > or = 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received > or = 63 Gy. CONCLUSION: With daily fractions of 1.7 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio.

Pulmonary metastases in children and young adults with differentiated thyroid cancer.

BACKGROUND: The prognostic significance and optimal care of children with differentiated thyroid cancer and pulmonary metastases are not well established. METHODS: Of 209 patients younger than 25 years of age who were treated at University of Texas M. D. Anderson Cancer Center between 1960 and 1990 and for whom there was sufficient information, 19 (9%) had pulmonary metastases at presentation. RESULTS: All of these patients had regional lymphadenopathy at the time of diagnosis. All but two had intense, diffuse radioiodine uptake in the lungs; there were two false-negative scans immediately after surgical procedure caused by competing thyroid residual. The chest radiograph (CXR) was normal in 8 of 17 (42%) patients with abnormal radioiodine scans. After therapy with radioiodine (100-499 mCi), CXR appeared normal in 7 of 9 patients with initial abnormal radiographs (within 6-75 months). Radioiodine uptake by the lungs normalized in 3 of 8 patients with initially normal radiographs, and in 3 of 9 patients with initially abnormal radiographs. There have been no deaths in these 19 patients. CONCLUSION: Pulmonary metastases are not uncommon in children and young adults with differentiated thyroid cancer, especially those who have regional lymphadenopathy. The lung metastases almost always concentrate radioiodine diffusely and may be associated with a normal CXR in almost half of the patients. Pulmonary metastases may be overlooked unless near total thyroidectomy is followed by total body radioiodine scan (TBS) in all children and young adults who have regional lymphadenopathy of the neck.

Carcinomas of the nasal cavity.

Between 1969 and 1985, 45 patients with carcinomas of the nasal cavity proper received curative treatment. Thirty patients had squamous cell carcinoma, one had undifferentiated carcinoma, 9 had adenocarcinoma, and 5 had adenoid cystic carcinoma. Eighteen patients were treated with definitive radiotherapy (interstitial brachytherapy in 5 and external beam therapy in 13 patients), and 27 received surgery and radiotherapy. The median length of follow-up was 11 years (range: 2.8-16.8 years). Thirty-six patients had no evidence of disease at the last follow-up visit. All 14 patients with carcinoma of the nasal septum had the disease controlled. Nine of 31 patients with lesions of the lateral wall and floor died of the disease, 5 of uncontrolled local disease, 2 of distant metastases, and 2 of both. The disease-specific survival rates at 5 and 10 years were 83 and 80%, respectively, and the corresponding overall survival rates were 75 and 60%, respectively. Blindness occurred in 4 patients, 2 due to orbital exenteration and 2 to radiation injury to the cornea and optic pathway. Other infrequent side effects were bone necrosis, dental decay, nasal stenosis, and septal perforation. This study indicated that the prognosis of patients with nasal cavity carcinoma was better than that of patients with maxillary sinus cancer treated during the same era. In addition, the study showed that carcinomas of the nasal septum were smaller than those of lateral wall and floor at diagnosis, so that excellent control could be achieved by definitive radiotherapy; when accessible, interstitial brachytherapy might be the treatment of choice in such patients.

Salivary gland neoplasms in children.

Of 29 patients, aged 3 to 16 years, with nonvasoformative salivary gland tumors, 21 had malignant tumors. Mucoepidermoid carcinoma was the most common; adenocarcinoma, adenoid cystic carcinoma, and acinic cell carcinoma were equally represented. Pleomorphic adenoma was the exclusive benign lesion, occurring in eight patients. Mean follow-up for patients with malignant lesions was 13.6 years (minimum, 3.5 years). Absolute 2- and 5-year survival rates were 100% and 90%, respectively. Mean follow-up for benign lesions was 15.9 years; none recurred. Superficial or total parotidectomy is the treatment of choice for malignant parotid neoplasms. Benign parotid lesions are adequately controlled with parotidectomy based on extent of disease. Facial nerve sacrifice can often be avoided. We advocate postoperative radiotherapy for high-grade lesions or those with adverse prognostic factors, such as soft-tissue extension and perineural invasion.

Prognostic variables in parotid gland cancer.

We performed a retrospective review of 178 previously untreated patients with primary malignant neoplasms of the parotid gland treated at our institution between 1960 and 1985. Patients were followed up for a median of 7.5 years. Fifty-nine percent underwent surgery alone, and 40% underwent surgery and radiation therapy. Univariate and multivariate analyses established the prognostic influence of cancer stage, cancer grade, histologic type, presence of lymphatic invasion, perineural invasion, tumor size, extension beyond the parotid gland fascia, cervical adenopathy, quality of margins, and patient age and gender. Survival was influenced most by tumor grade, tumor size, presence of positive cervical lymph nodes, and facial nerve invasion. The risk of local-regional recurrence was most affected by cervical adenopathy and tumor size. Distant metastases were predicted by tumor grade and size. At last contact, 39% of patients were alive and free of disease, while 26% had died of the disease. We analyzed the optimal surgical procedure and the rationale for the selection of combined treatment.

Primary sarcomas of the major salivary glands.

Sarcomas arising in the major salivary glands are rare. This article presents the clinicopathologic features of 11 patients with primary sarcomas of the parotid gland (eight men and three women aged 7 to 75 years; mean age, 42 years). The 11 sarcomas were histologically typified as follows: three malignant fibrous histiocytomas and two each of neurosarcomas, rhabdomyosarcomas, fibrosarcomas, and osteosarcomas. Four patients experienced disease recurrences, and seven patients developed metastases. Seven patients died of their sarcomas, with a mean survival time of 30 months. Four patients were alive from 5 to 12 years (one each with angiomatoid malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, fibrosarcoma, and neurosarcoma). Prognosis correlated with size of the neoplasm, type of sarcoma, and histologic grade. In this respect, salivary gland sarcomas behaved in identical fashion to their soft-tissue counterparts.

Lymph node metastasis from papillary-follicular thyroid carcinoma in young patients.

A total of 117 patients under 20 years of age with papillary and/or follicular thyroid cancer presented to the M. D. Anderson Cancer Center between 1949 and 1987. The most common presenting symptom was a cervical mass. Twenty percent of the patients had a history of prior irradiation. Sixty percent initially had palpable lymph nodes, while 26% who had clinically negative examinations had pathologically positive lymph nodes. Recurrence was highest in regional lymph nodes at 24%, with only a 4% recurrence rate at the primary site and a 3% recurrence rate at distant sites. There were no deaths due to the thyroid cancer. To maintain a low rate of recurrence, near-total thyroidectomy with neck dissection followed by iodine 131 treatment should be considered in these young patients.