Ronald H. Spiro

Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases.

In recent years, the term “adenoid cystic carcinoma” has won increasing acceptance as the one preferred for the unusual, malignant epithelial tumor that Billroth called “cylindroma” in 1856 [I-7]. Whatever the preference in nomenclature, neoplasms showing an adenoid cystic histologic pattern are quite uncommon and may arise in a variety of anatomic sites, including the paired salivary glands, the lacrimal gland [8,9], the mucous glands of the upper respiratory [IO] and digestive tracts [11,12], the skin [13,14], and the breast [15,16]. In this study, we shall focus on a sizable experience with adenoid cystic carcinoma arising in major and minor salivary (mucous) glands. Patients having similar tumors in the lacrimal glands or mucous glands of the trachea have been excluded, although other reports suggest that the clinical course is similar [8,10]. The designation of certain rare skin and breast tumors as “adenoid cystic” is somewhat misleading, inasmuch as the clinical course in such patients is quite different.

Distant metastasis in adenoid cystic carcinoma of salivary origin

BACKGROUND Adenoid cystic carcinoma (ACC) is an aggressive, often indolent tumor, with a high incidence of distant metastasis (DM). Relatively little has been written about the factors that influence distant spread and subsequent survival because it is uncommon and more than a decade of observation may be required to appreciate the prolonged clinical course in some patients. METHODS We have retrospectively studied 196 determinate patients who received definitive treatment in our hospital between 1939 and 1986 for ACC in all salivary sites. Inclusion criteria were no prior treatment elsewhere other than excisional biopsy and eligibility for follow-up of at least 10 years. Variables assessed for their impact on distant metastasis included age, gender, site, size, node status, stage, grade, and locoregional treatment failure. RESULTS Treatment failure occurred in a total of 122 of 196 determinate patients (62%), 74 of whom had DM (38%). This was usually associated with locoregional recurrence (51 patients), but DM was the only indication of failure in 23 whose primary tumor was controlled. Of the 74 patients with known DM, the lung was recorded as the only involved site in 50 patients, lung was involved in addition to other sites in 17, bone metastases alone occured in 5, and the remaining 2 developed disseminated disease. Disease-free intervals varied from 1 month to 19 years (median 36 months) and exceeded 10 years in 9 of 113 patients (8%) with adequate information about treatment failure. Survival with DM was less than 3 years in 54%, but more than 10 yrs in 10% (maximum 16 years). The only significant factors influencing survival were the size of the primary tumor (P <0.0000), local or neck recurrence (P = 0.0006), and the presence of nodal involvement (P = 0.02). CONCLUSIONS The high incidence of DM with locoregional failure confirms the importance of aggressive initial surgery, combined with irradiation, for high-stage tumors or involved surgical margins. Large tumor size and lymph node involvement, rather than microscopic appearance, were predictive of DM. Considering that lung metastases are usually multiple, and prolonged survival without treatment is not unusual, resection of pulmonary metastases may be hard to justify in ACC patients based on the limited experience thus far reported. Chemotherapy for metastatic ACC is probably best withheld until symptoms appear.

The indications for elective treatment of the neck in cancer of the major salivary glands

To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982, Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors [P < 0.00001). High‐grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate‐grade or low‐grade tumors [P < 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High‐grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

Cervical node metastasis from epidermoid carcinoma of the oral cavity and oropharynx: A critical assessment of current staging☆

Abstract The clinical and histologic status of cervical lymph nodes has been correlated with the results of treatment in 1,069 consecutive patients who underwent radical neck dissection as part of the initial treatment of a primary epidermoid carcinoma arising in either the oral cavity or oropharynx. The influence on “cure” rates of size, number, location, and fixation of involved nodes, correlated with the specific site of origin within the oral cavity, was evaluated in determinate patients with proved nodal metastasis. As the extent of lymph node involvement increased from solitary to multiple ipsilateral and to bilateral enlarged nodes, cure rates dropped progressively. Survival was not invariably decreased in those whose involved nodes were large or considered fixed, and there was considerable variance among examiners when size and fixation were evaluated. These data suggest that the N system of staging presently advocated might be improved. Rather than designating contralateral or bilateral node involvement as N 2 , this category might be reserved for those with multiple ipsilateral cervical node metastases. Those with contralateral and bilateral as well as so-called fixed metastases might better be relegated to the N 3 category. The results of treatment were uniformly poor in the latter group of patients, provided the term “fixed” indicated immobility of involved lymph nodes and not merely the presumption that tumor had extended beyond the capsule of the node.

Pattern of invasion and margin assessment in patients with oral tongue cancer

Involvement of resection margins and the pattern of tumor invasion are reported to be important predictors of local recurrence and survival in surgically treated patients. In this study we have retrospectively assessed the significance of these two prognostic factors in a relatively homogeneous patient population.

Acinic cell carcinoma of salivary origin. A clinicopathologic study of 67 cases

This study reviews a 30 year experience with acinic cell carcinoma. The tumor arose in the parotid gland in 64 patients, the submaxillary gland in one and minor salivary glands in two. In untreated patients with small tumors, clinical findings usually suggested a benign mixed tumor and a subtotal parotidectomy which spared the facial nerve was highly effective therapy. In contrast, local recurrence and death was the rule in those few who had locally extensive disease, regardless of how radical an operation was performed. Determinate “cure” rates for the entire group were 76, 63 and 55% at 5, 10 and 15 years, respectively. Cervical lymph node metastasis occurred in 16% of the patients, and distant metastasis in 12%. Survival was most directly influenced by the clinical extent of the primary tumor, and also correlated with certain histologic features which are described.

Critical assessment of supraomohyoid neck dissection

During a recent 5-year period, 115 patients had 131 supraomohyoid neck dissections. Eighty-one percent of these procedures were performed for squamous carcinoma. Seventy-nine percent of the primary tumors were located in the oral cavity and 16 percent arose in the oropharynx. Almost 80 percent of the necks dissected for primary squamous carcinoma were clinically N0, and occult nodal disease was discovered in 31 percent of these neck specimens. When the supraomohyoid neck dissection specimen showed no involvement, the overall incidence of treatment failure in the neck at 2-year follow-up was 5 percent. Almost all patients with occult squamous carcinoma in the supraomohyoid neck dissection specimen received postoperative radiotherapy, and the failure rate in the neck was 15 percent. When neck nodes were both clinically and pathologically involved, neck recurrence developed in 29 percent of the patients despite the addition of adequate postoperative radiotherapy. Among those patients with nonsquamous primary tumors and a pathologically negative supraomohyoid neck dissection specimen, there was only one subsequent treatment failure in the neck. Supraomohyoid neck dissection appears to be a valid staging procedure for clinically N0 patients with primary squamous carcinomas located in the oral cavity or oropharynx, with an appropriate yield of occult nodal disease, and infrequent treatment failure in the dissected neck when the supraomohyoid neck dissection specimen is pathologically uninvolved. When nodal disease is clinically obvious, treatment failure is more frequent, even with the addition of postoperative radiotherapy. The role of supraomohyoid neck dissection in this setting deserves further study.

Combination therapy of advanced head and neck cancer. Induction of remissions with diamminedichloroplatinum (II), bleomycin and radiation therapy

Patients with unresectable, previously untreated head and neck cancer were given cis‐diamminedichloroplatinum (II) (DDP), 3 mg/kg, with mannitol diuresis (day 1), followed by a continuous infusion of bleomycin, 0.25 mg/kg/day, days 3 through 10, after an initial loading dose of 0.25 mg/kg by rapid IV injection on day 3. The DDP was repeated on day 22, following which radiotherapy was delivered using standard doses, fractionations and portals. Patients were evaluated for response on day 22 and again at the conclusion of radiotherapy. Of 21 patients evaluable at day 22, there were four CR and 11 PR (>50% reduction of all measurable disease), for a major response rate of 71%. Of five MR, four showed 30–60% reduction at the primary site. Of 16 who have finished the radiation phase of treatment, there are six CR, five PR and one MR with durations four to eight months. Toxicity in 33 patients included vomiting (33), alopecia (33), WBC < 3000 (five), platelets lt; 100,000 (one), dose‐limiting mucositis during bleomycin (six) and peak serum creatinine > 2 (five), with one fatality. The regimen thus appears promising as initial therapy for the previously untreated patient. The same chemotherapy has produced much less encouraging results in previously treated patients.

Malignant mixed tumor of salivary origin. A clinicopathologic study of 146 cases

A 30‐year Memorial Hospital experience with 146 patients with malignant mixed tumor is reviewed. These comprised 5% of 2,743 patients who were treated for salivary neoplasms from 1939 through 1968. The tumors arose in the parotid gland in 108 patients, submaxillary gland in 23 patients, mucus or so‐called minor salivary glands in 16 patients, and sublingual gland in one. In terms of our total experience, 11% of all submaxillary tumors proved to be of the malignant mixed variety as compared to 6% of parotid tumors and 3% of minor salivary tumors, respectively. Seventy‐one patients (48%) had previously received therapy elsewhere. Results of treatment are presented and the factors which influenced the results are discussed.

Carcinoma of the hypopharynx

The data in this study suggest that radical surgical treatment offers the best chance for control of disease in patients with cancer of the hypopharynx. The cervical lymph nodes are at a very high risk for early involvement by metastatic disease. Elective treatment of cervical lymph nodes must be considered in initial treatment planning to obtain better control of regional disease.