Relationship of depth of invasion to survival outcomes and patterns of recurrence for T3 oral tongue squamous cell carcinoma.

INTRODUCTION: Current research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI. OBJECTIVES: Determine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10-20 mm). METHODS: Retrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified. Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology. Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy. Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm). RESULTS: One hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18-80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis. CONCLUSION: DOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients.

Mucoepidermoid carcinoma of the parotid gland: a rare presentation in a young child.

Although mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland neoplasm in childhood and adolescence, it is rarely found in children under the age of 10. A 6-year-old girl had an asymptomatic neck mass for 5 months. Clinical examination findings showed a 1.5-cm smooth and firm but mobile nontender mass located in the upper left anterior cervical triangle, clinically separate from the parotid gland. Ultrasound examination findings showed a vascular mass, with a cystic component, possibly within the tail of the parotid gland. An excisional biopsy was performed and frozen section showed a low-grade MEC. A left superficial parotidectomy was then performed. Final histopathologic examination showed one positive resection margin. Subsequently, reexcision of the surgical site and an upper modified neck dissection was undertaken. This unusual presentation of MEC as a neck mass in one of the youngest reported patients illustrates that the anatomic region for parotid tumors is large. Possibly some of these tumors may arise from heterotopic or accessory parotid tissue.

Parathyroid cancer: clinical variations and relationship to autotransplantation.

OBJECTIVE: To identify the clinical and pathological characteristics of parathyroid cancer to determine the best method of treatment and to prevent the use of malignant tissue for autotransplantation. DESIGN: A chart review over a 20-year period (1973 to 1993). SETTING: Two tertiary-care referral centres in Ontario with specialty interest in disease of the thyroid and parathyroid glands. PATIENTS: Sixteen patients, identified as has having parathyroid cancer (equivocal diagnosis in 9 and definitive diagnosis in 7). MAIN OUTCOME MEASURES: The clinical and histologic features, treatment, morbidity and mortality of parathyroid cancer. RESULTS: Some patients with an equivocal diagnosis had postoperative recurrent hyperparathyroidism characterized by multiple soft-tissue implants of parathyroid that persisted after reoperation. The others had infiltrative attachment of parathyroid lesions to the thyroid gland and were eucalcemic and disease free up to 12 years after treatment. Three of the seven patients with a definitive diagnosis of parathyroid cancer were treated for a neck mass; the others were treated for hypercalcemia and multiple lytic bone lesions, hypercalcemia and renal disease and secondary hyperparathyroidism. En-bloc resection, carried out in all but one case, was curative in five cases. The patient with secondary hyperparathyroidism underwent total parathyroidectomy and autotransplantation but died of metastatic parathyroid cancer 1 year later. CONCLUSIONS: Because of the difficulty in making a histologic diagnosis of parathyroid cancer, en-bloc resection of the thyroid and parathyroid glands and locally invaded structures is the appropriate treatment to avoid tumour spillage. Caution should be exercised in the use of donor parathyroid tissue for autotransplantation.

Postlaryngectomy quality-of-life dimensions identified by patients and health care professionals.

We compared the quality-of-life (QOL) dimensions after laryngectomy in patients with advanced larynx or pharynx cancer that were elicited from 20 consecutive laryngectomy patients and 20 health care professionals working in the Regional Head and Neck Oncology Service. Subjects in both groups were asked to identify important QOL items after recovery from laryngectomy and to rank and rate each on a vertical visual analogue scale. Health care professionals ranked impaired communication and self-image/self-esteem as the two most important QOL dimensions, whereas patients ranked the physical consequences of surgery, e.g., tracheal mucous production, and interference with social activities as the two most important items. The results indicate that the responses of health care professionals do not fully correlate with patient priorities. These findings are relevant to researchers developing treatment-specific QOL measures and to health care professionals when presenting treatment options to patients.

Optimal conditions for immunohistochemical determination of the in vitro DNA synthesis labelling index with bromodeoxyuridine in head and neck cancer.

The in vitro DNA synthesis labelling index was assessed immunohistochemically in 24 freshly obtained specimens of head and neck cancer using bromodeoxyuridine (BrdUrd) as the DNA precursor to determine the influence of BrdUrd concentration on labelling index (LI). Initially, tumour fragments were incubated in varying concentrations of BrdUrd from 2 to 100 microM for 2 h, and BrdUrd was detected with an anti-BrdUrd monoclonal antibody using immunoperoxidase labelling. There was a dose-response gradient with mean LI varying from 1.6% at 2 microM BrdUrd to 8.8% at 100 microM. The concentration-response gradient best fit a quadratic model when LI was plotted against log BrdUrd concentration (r = 0.65, P less than 0.0001). Eleven additional tumours were then studied to determine whether LI increased for BrdUrd concentrations above 100 microM. The mean LI at 125 microM and at 150 microM in these 11 tumours did not differ from the value at 100 microM, suggesting a plateau at this level. The gradient effect accounted for 17% of the variance in LI, while 60% of the variance was explained by between tumour differences. Within individual tumours, three response patterns were observed: (i) LI rose at a constant rate to the highest concentration tested (n = 8), (ii) the LI plateaued or declined at high BrdUrd concentrations (n = 6); and (iii) there was a biphasic slope slope in which the rate of rise in the LI increased at the higher BrdUrd concentrations (n = 2). The data show that BrdUrd concentration is an important variable in the immunohistochemical assessment of the in vitro LI in head and neck cancer.

Sternocleidomastoid flap following parotidectomy.

The sternocleidomastoid (SCM) muscle has been used in various ways for reconstruction following cancer resections in the head and neck. Its use has been restricted because of the presumed precarious nature of its blood supply and its proximity to disease. Patients with large or recurrent benign parotid tumors were the first in our series to have a SCM muscle flap (either superiorly or inferiorly based) used to improve cosmesis. After demonstrating the utility of these flaps, we extended the indications for their use to include patients with primary or recurrent malignant disease. The flaps provide soft tissue contour, coverage of facial nerves and nerve grafts, act as a healthy bed for skin grafts, and help close salivary fistulas. There were no complications attributed to the flaps. This paper discusses 31 patients with benign and malignant parotid disease in whom the SCM flap was used.

Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: a randomized placebo-controlled clinical trial.

Randomized trials comparing high-dose methotrexate (HDMTX) plus leucovorin (LV) with standard-dose methotrexate (SDMTX) have not detected a therapeutic advantage for the HDMTX arm despite compelling evidence from experimental systems. We hypothesized that these negative trials might reflect modulation of the antitumor effect of methotrexate (MTX) by LV. To test this we randomized 61 patients with locally advanced and recurrent squamous cell head and neck cancer to receive SDMTX (40 mg/m2 weekly for 8 weeks) and either LV or placebo "rescue" starting 24 hours later. Of the 61 randomized patients, there were protocol violations in two cases, leaving 59 patients evaluable for response using standard criteria, and for toxicity using the Eastern Cooperative Oncology Group (ECOG) scale. Of the 29 patients randomized to MTX plus LV, there were five responders (17.2%) compared with 11 of 30 (36.7%) patients randomized to MTX plus placebo (P = .047). Response was influenced independently by age, gender, and by previous treatment. Toxicity overall was more severe in patients randomized to MTX plus placebo (P = .016). This was accounted for primarily by differences in toxicities related to bone marrow function (neutrophil and platelet counts), stomatitis, and elevations of liver function tests. MTX therapy was more often interrupted for toxicity in the placebo group (P = .007) and discontinued for progressive disease in the LV group (P = .07). These results indicate that at the doses of MTX and LV used, LV modulates the antitumor effect as well as the toxicity of MTX in patients with head and neck cancer.

Methotrexate/fluorouracil scheduling influences normal tissue toxicity but not antitumor effects in patients with squamous cell head and neck cancer: results from a randomized trial.

To test the hypothesis that sequential scheduling of methotrexate (MTX) and fluorouracil (FU) produces a synergistic antitumor effect, we randomized 113 patients with recurrent or locally advanced squamous cell carcinoma of the head and neck to receive MTX-FU either 18 hours apart or simultaneously, with leucovorin rescue. There were 100 patients with locally advanced newly presenting disease and 13 patients with recurrence. Excessive toxicity was observed in the first 11 patients who received MTX 250 mg/m2 administered intravenously (IV) and leucovorin at 36 hours, therefore all subsequent patients received MTX 200 mg/m2 administered IV and leucovorin at 24 hours. FU 600 mg/m2 IV was administered to all patients, and treatment was given on days 1 and 8 of 21-day cycles. The treatment groups were well balanced for known prognostic variables. The response rate was 47.3% (26 of 55) for simultaneous v 44.8% (26 of 58) for sequential therapy. These results exclude a 20% difference in response rate favoring sequential therapy at P = .04. There was no observed difference in survival between the two treatment arms (P = .55) with a minimum follow-up of 8 months. Toxicity was greater in patients who received sequential therapy, and the difference was confined to the gastrointestinal (GI) tract. A comparison of the distribution in maximum Eastern Cooperative Oncology Group (ECOG) toxicity scores during chemotherapy for the two treatment groups showed greater stomatitis (P = .001), diarrhea (P = .04), and overall toxicity (P = .02) for sequential treatment without an observed difference in bone marrow toxicity. The results of this trial indicate that sequential MTX-FU is not superior to simultaneous therapy for the treatment of patients with head and neck cancer. Biochemical modulation of MTX-FU by drug scheduling may occur in vivo and may be organ specific.

Sebaceous carcinoma of the face following irradiation.

Malignant neoplasms of sebaceous glands are uncommon but generally occur about the head and neck, where these glands are concentrated. The sites of most frequent occurrence are the ocular adnexae, where sebaceous carcinoma presents as an infiltrating malignancy with a poor prognosis. Cutaneous sebaceous carcinoma is rare at other sites but has a better prognosis. We have located eight cases in the literature of sebaceous carcinoma arising in a previously irradiated field: five in the ocular adnexae and three elsewhere on the face. We here report a fourth case of recurrent sebaceous carcinoma with metastases that occurred on the face of an 82-year-old woman who had received radiation to the area for cosmetic epilation 35 years previously.

Diagnostic accuracy of fine-needle aspiration biopsy versus frozen section in solitary thyroid nodules.

Fine-needle aspiration biopsy is widely used in the diagnosis and management of the solitary thyroid nodule. It is the most accurate tool available and decreases the need for ultrasonography and thyroid scanning. In those patients who are selected for surgical treatment by fine-needle aspiration biopsy, it has been advocated as a guide to determining the extent of operation. Frozen section, which usually serves as the surgeon's guide, and fine-needle aspiration biopsy both have varying accuracy rates. Few direct comparisons have been made. We studied 198 aspirates in 198 patients who presented with a solitary nodule and had surgical excision. Fine-needle aspiration biopsy (198 cases) and frozen section (182 cases) were compared with the final histologic diagnosis. Accuracy rates for fine-needle aspiration biopsy and frozen section were 90 percent and 95 percent, respectively. Fine-needle aspiration biopsy detected 43 percent of the cancers and frozen section, 64 percent. There were no false-positive diagnoses with frozen section, but three cases with fine-needle aspiration biopsy. The false-negative diagnosis rate was 5 percent for frozen section and 8.5 percent for fine-needle aspiration biopsy. When the "other" diagnosis category was grouped with the "positive" diagnosis category and a single expert cytopathologist was used to read the cytology report, the sensitivity was increased to 80 percent whereas the accuracy was maintained at 83 percent. We believe that since there were no false-positive diagnosis using frozen section, it can reliably be used as a guide when it reveals malignancy. When the fine-needle aspiration biopsy diagnosis is "positive" or "other," it can guide operation, but only after carefully assessing the wording of the cytology report and the clinical situation. Each modality can provide information missed by the other. We continue to use them as complementary tools in the diagnosis and management of solitary thyroid nodules.

Survival results from a phase III study of simultaneous versus 1-hour sequential methotrexate-5-fluorouracil chemotherapy in head and neck cancer.

There were 79 patients with squamous cell head and neck cancer randomized to receive simultaneous or 1 hour sequential methotrexate-5 fluorouracil (MTX--5-FU) chemotherapy: 47 patients were previously untreated and 32 patients had recurrent disease. The treatment groups were comparable for important prognostic features. The median survival for the 47 newly presenting patients was 22 months and for recurrent disease patients was 14 months. No difference could be detected in the survival of patients who received simultaneous versus sequential chemotherapy. When only chemotherapy responders were compared, no difference in survival was detected for those who received sequential versus simultaneous therapy. Subsequently, 19 chemotherapy responders received radical radiation therapy, and 15 were rendered disease-free whereas only 4 of 17 chemotherapy nonresponders were rendered disease-free by subsequent radiation (P = .002). The survival of the 19 chemotherapy responders was 34 months compared with 16 months for the 17 chemotherapy nonresponders treated with radiation. We conclude that there is no therapeutic advantage for 1 hour sequential MTX-5 FU chemotherapy compared with simultaneous use of these drugs in squamous cell head and neck cancer. Chemotherapy responders are more likely to respond to radiation therapy.

Fine needle aspiration biopsy cytology of major salivary glands.

Fine needle aspiration biopsy of the major salivary glands was performed on 160 patients. In 146 patients with satisfactory samples, the cytologic diagnosis was correlated with clinical follow-up and histologic findings. There were 122 benign lesions, including 47 tumors. There were 24 malignant lesions, 10 of which were primary and 14 metastatic. The overall accuracy was 98%. The sensitivity of the technique was 87.5%. There was no false-positive diagnosis. There were three false-negative diagnoses due to sampling errors and inexperience during the initial period of the study. This study documents that needle aspiration biopsy cytology of the salivary glands is accurate, simple, rapid, inexpensive, well tolerated and harmless to the patient.

Aspiration biopsy cytology of lymph nodes in malignant lymphoma.

The cytologic findings of needle aspiration biopsy of lymph nodes in malignant lymphoma are presented. In 42 of 49 cases, a correct cytologic diagnosis was rendered. There was one false-positive diagnosis. The diagnostic accuracy of needle aspiration cytology is high. It helps to select patients for further investigation and treatment, thereby avoiding unnecessary surgery in patients who present with lymphadenopathy. The technique is also useful in the staging work-up of patients with lymphoma and the diagnosis of recurrent disease during the follow-up period.

Needle aspiration cytology of sebaceous carcinoma.

Sebaceous carcinoma is uncommon and usually presents in the ocular adnexae as cancer of the meibomian glands. That cutaneous sebaceous carcinoma generally occurs along with other epidermal elements has caused some nosologic confusion; tumors in which sebaceous elements predominate are encountered rarely. They are aggressive tumors in any location but particularly around the ocular adnexae, necessitating wide excision and careful follow-up to detect metastases. At our institution two such tumors were excised recently, one from the eyelid and one from previously irradiated skin. Subsequent metastases were detected without difficulty on needle aspiration cytology, which produced characteristic epithelial cells with bubbly , lipid-rich cytoplasm. The cytologic, histologic and ultrastructural appearances of these tumors that are suited to diagnosis on fine needle aspirates are reported.

Needle aspiration cytology of a benign and a malignant schwannoma.

The histologic and cytologic features of an uncommon solitary, malignant schwannoma and a benign schwannoma are presented. The benign tumor revealed characteristic interlacing fascicles of spindle-shaped cells on both histology and cytology. The malignant schwannoma produced a variable histologic pattern that was selectively sampled from a recurrence in a scar; only obviously malignant, undifferentiated, spindle-shaped cells not capable of further characterization were seen on cytology. Preliminary experience with immunoperoxidase staining for the neural crest marker S-100 protein has been encouraging and may permit identification of these tumors on aspiration smears.

Prospective randomized trial of one-hour sequential versus simultaneous methotrexate plus 5-fluorouracil in advanced and recurrent squamous cell head and neck cancer.

Results from experimental systems suggest that the combination of methotrexate (MTX) and 5-fluorouracil (5-FU) produces synergistic cytotoxic effects that are dependent on the sequence of drug administration. Biochemical studies have demonstrated plausible mechanisms of a synergistic effect when MTX precedes 5-FU. A variety of phase I and phase II studies have employed this sequential combination with promising but inconclusive results. In this study, 79 evaluable patients with squamous cell head and neck cancer were randomized to receive MTX (200 mg/m2 IV) and 5-FU (600 mg/m2 IV) either simultaneously or sequentially with MTX preceding 5-FU by one hour. All patients were ambulatory and patients were stratified as to whether they presented with primary disease or with recurrence after prior radiation and/or surgical therapy. The overall response rate was superior for simultaneous therapy (62%) compared with sequential therapy (38%) (p less than 0.06). Among patients with primary head and neck cancer, the stage of the disease influenced the response rate. Eight of nine stage III patients who received simultaneous therapy responded while none of the four patients who received sequential therapy responded (p less than 0.01). This study demonstrates that one-hour sequential MTX plus 5-FU is not superior to simultaneous treatment in patients with squamous cell head and neck cancer.

Fine needle aspiration biopsy cytology of paragangliomas. Cytologic, light microscopic and ultrastructural studies of three cases.

Paragangliomas are uncommon tumors arising in paraganglion tissue, which is especially well represented in the head and neck. In our hospital three head and neck masses recently proved to be paragangliomas on aspiratory biopsy cytology, with subsequent histologic confirmation. One was an apparently benign carotid body tumor, while the others were metastatic nasopharyngeal paragangliomas. The latter two tumors were clearly malignant, with roentgenographically proven pulmonary metastases in one and widespread lymph node involvement in the other. Histologically all were vascular tumors composed of large cells with abundant cytoplasm and pleomorphic, sometimes bizarre nuclei. These characteristic chief cells were clearly evident on cytology, with pleomorphic nuclei, prominent nucleoli, clumped chromatin and generally eosinophilic, finely granular or reticular cytoplasm. However, the distinction between benign and malignant tumors depended on the presence of mitoses or a tumor diathesis. Cytology seems to be able to provide a diagnosis of paraganglioma and, in these cases at least, an estimation of the biologic behavior.

Needle aspiration cytologic biopsy in head and neck masses.

Over 500 fine (no. 22) needle aspiration biopsies were done on head and neck lesions. The total accuracy for the series was 94.5 percent. The accuracy rates for thyroid, salivary and metastatic or benign lymph node lesions were similar: approximately 95 percent. Only lymphomatous lesions gave a lower accuracy rate: 75 percent. This method of evaluating masses in the head and neck is simple, rapid, inexpensive, well-tolerated and harmless, and is very accurate when there is close cooperation between the clinician and the cytopathologist.

Early surgical management of acute cholecystitis.

Between 1971 and 1977, 361 patients underwent early elective cholecystecomy for acute cholecystitis, and the complications and mortality were studied according to the length of time from admission to operation. A substantially greater proportion of the complications, and the only deaths, occurred in the patients operated upon more than 7 days after admission. The mortality rate was 0.6%. Nine additional high-risk patients underwent cholecystostomy. There were four postoperative deaths in this group, all related to the debilitating underlying conditions. The mortality for the entire series was 1.6%. These results compare favourably with those following delayed elective operations for acute cholecystitis. Early elective operation, using cholecystectomy when possible and cholecystostomy when necessary, is recommended for general use in experienced hands. This practice is safe and sound particularly when the diagnosis is made more certain preoperatively by the use of intravenous cholangiography.