Cervical lymph node metastases from an unknown primary

In!. J. Radiation Oncology Biol. Phys., Vol. 5. pp. 73-76 @ Pergamon Press Inc., 1979. Printed in the U.S.A.

03bCL3016/79/0101-0073/$02.00/0

??Brief Communication

CERVICAL LYMPH NODE METASTASES FROM AN UNKNOWN PRIMARY DONALD

G. NORDSTROM, M.D., HAMED H. TEWFIK,M.B.,Ch.B ., M.D. and HOWARDB. LATOURETTE, M.D.

Department of Radiation Therapy, University of Iowa, Hospitals and Clinics, Iowa City, IA 52242, U.S.A. In this retrospective study covering tbe period from 1960 to 1973, a series of 51 patients were treated at the University of Iowa Hospitals for cervical lymph node metastases from an occult primary. Of this group of 51 patients, 27 (53%) survived 2 years and 15 (2!WG)survived 5 years. The best control and prognosis occurred in those patients who had a radicai neck dissection combined with radiation therapy consisting of at least 5OOtlrad to the entire neck and to the sites of a potential ENT primary. The dose of radiation therapy given to the contraiaterai neck prevented later appearance of nodes and was effective in eliminating the appearance of the primary cancer in the naso-oro-iaryngopharyngeai region. Foiiow-up of our patients eventually yielded only 1 ENT primary, and 6 patients eventuaiiy demonstrated a lung primary as the cause of their cervical lymph node metastases. Unknown primary,

Cervical node metastases,

Carcinoma

INTRODUCTION

METHODS

AND

MATERIALS

This retrospective study covers the period from 1960 to 1973; a total of 103 patients were evaluated at the University of Iowa Hostpitals for metastases to cervical nodes with no obvious source. Charts of these patients were reviewed and analyzed. The primary was determined in 33 patients (33.04%) after careful search. The most common source was the lung (7 patients), followed by the larynx (4 patients) and then the colon, lip and lymphoma (3 patients each). The ear and parotid glands were determined as the source in 2 patients each; the oropharynx, salivary glands, brachial cleft tumor, floor of mouth, tongue, pyriform sinus, eyelid, melanoma and bladder were determined as the source for 1 patient each. The primary source of the neck metastases could not be found in the remaining 70 patients (67.96%). Of this group, 18 were excluded for the following reasons: therapy was given elsewhere (8 patients), death occurred during treatment (2 patients), such extensive tumor bulk that therapy was not attempted (7 patients) and refusal of any form of therapy (2 patients). The remaining 51 patients were diagnosed to have metastases to cervical lymph nodes with no

The patient with carcinoma that involves the cervical lymph nodes and has no apparent origin is a diagnostic challenge. In previously reported studies, the incidence of such cases of metastatic nodes of the neck has ranged from 1.8% to 9% of the total head and neck neoplasms.3P4,7 A careful and thorough search to find the primary must be performed. If this search for an origin is unsuccessful, these patients still warrant aggressive therapy; surgery and radiation therapy may control these lesions. In addition to careful examination of the ENT system, diagnostic evaluation should include direct laryngoscopy with bronchoscopy and esophagoscopy. Biopsy should be performed on any suspicious lesions in addition to routine washings for cytologic evaluation. Even though the nasopharynx, base of tongue, tonsils and pyriform sinus may appear normal, these areas should be biopsied since they may be the site of an occult neoplasm. Diagnostic surveys also include a chest X-ray, para-nasal films, upper gastrointestinal barium study, barium enema and intravenous pyelogram. Any suspicious areas can be examined further with tomograms or computerized tomography (CT) scanning when appropriate.

Reprint requests to: Donald G. Nordstrom, M.D., 1417 South Minnesota Avenue, Acknowledgements-The

of the neck.

gomery for her assistance in the preparation manuscript. Accepted for publication 31 May 1978

Sioux Falls, SD 57105, U.S.A. authors thank Laurie Mont73

of

this

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primary demonstrated. This represents 2.1% of the patients with head and neck neoplasms who were seen at our institution from 1960 to 1973. The age of the patients ranged from 13 to 88 years with an average of 60 years. There was a male to female predominance of 40 : 11. Nearly all of the patients presented initially with the complaint of a neck mass. Additional symptoms included pain, weight loss and drainage from the lesions. The duration of the mass ranged from 2 weeks to 3 years before the patient consulted a physician; the usual delay was 4-6 weeks. In most instances, the patients received a complete diagnostic work-up which included roentgenographic and endoscopic studies of the gastrointestinal tract, intravenous roentgenographic and pyelography, endoscopic examination of the upper and lower part of the respiratory tract and biopsies as indicated. Pathological examination showed that epidermoid carcinoma was the predominant type (36 of 51 patients). Thirteen patients were diagnosed as having anaplastic carcinoma, and 2 patients were diagnosed with adenocarcinoma. Staging of the Table 1. Staging system for patients with cervical metastases from an unknown primary N, = Previously excised node-no gross residual N, = Single, moble node less than 3 cm N2 = A single, mobile node greater than 3 cm or multiple mobile ipsilateral nodes N, = Fixed unilateral node(s) or bilateral fixed or non-fixed nodes Table

Stage NX N, N2 N3 Total

2. Classification of patients treatment techniquet Surgery

Radiation

1 3

therapy

by

stage

Combined

:

0 1 6 10

1 2 7 12

12

17

22

tTotal number of patients

and

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patients was done according to the staging system shown in Table 1. Patients were treated with radiation therapy alone, surgical resection alone, or a combination of both these modalities. Table 2 presents a breakdown of patients by stage and treatment technique. The 34 patients who underwent surgery received a radical neck dissection on the involved side, whether it was the only treatment or combined with irradiation. Among the 22 patients who received a combination of irradiation and surgery, 4 received radiation therapy preoperatively and 18 postoperatively. In the patients with extensive disease or poor general condition, palliation was the goal of treatment; radiation therapy was delivered to the tumor mass with a limited field in 19 patients. Curative radiotherapy was employed in the remaining 20 patients. Treatment portals consisted of parallel laterally opposed fields to cover all of the neck, including the nasopharynx, oropharynx, tonsil, base of tongue and hypopharynx. The posterior extent covered the nodes of the posterior triangle. These two laterally opposed fields were treated to a midline total tumor dose of 5000 rad in 5-6 weeks. An anterior field to cover the lower cervical nodes was treated to a total tumor dose of 5000 rad at a depth of 3 cm below the skin over a period of 5-6 weeks. After 5000 rad were delivered the lateral portals were reduced in size to cone on the nasopharynx, base of tongue and pyriform fossa regions, avoiding the spinal cord, an additional dose of 1600 to 2000 rad was delivered over 2 weeks. The group treated surgically consisted of a greater proportion of patients whose disease was in early stages; the group treated with radiation alone or combined with surgery had a higher proportion of patients with disease in less favorable stages. RESULTS Tables 3 and 4 present 2 and 5 year survival rates. Since the majority of patients with extensive disease or poor general condition received radiation therapy only, this selection influenced the results with patients who were predetermined for poor survival.

is 51.

Table 3. Two year survival in relation to treatment

Stage

Surgery only No. (%)

Radiation therapy only No. (%)

modalities

Combined surgery and radiation therapy No. (%)

:: Ns

l/l 213 415 213

(loo) (66) (80) (66)

o/o O/l l/6 4/10

(0) (0) (17) (40)

l/l 212 717 3112

(loo) (100) (100) (25)

Total

9/12

(75)

5117

(29.4)

13122

(59.1)

NX

Cervical lymph node metastases from an unknown primary 0 D. G. NORDSTROM et al.

Table 4. Five year survival of patients with no evidence

Surgery only No. (%)

Stage NX NI N* N, Total

Radiation therapy only No. (%)

Combined surgery and radiation therapy (%) No.

N2 N3

Total (%)

o/o O/l l/6 3110

(0) (0) (17) (30)

l/l l/2 317 l/12

(100) (50) (43) (8)

212 316 6/18 4125

(100) (50) (33) (16)

5112

(41.7)

4/17

(23.5)

6122

(27.3)

15/S 1

(29.4)

eventually demonstrated a lung primary as the cause of their cervical lymph node metastases. These patients received radiation and/or resection of this primary, but cure was not achieved; the longest survival after detection of primary was 1 year. Autopsy was performed on 7 patients; 4 patients had lung cancer and 1 had cancer of the larynx. No evidence of tumor was noted in 2 patients. An additional patient was found to have a bladder cancer 7 years later. Unfortunately, only a few patients underwent autopsy in an attempt to determine the primary or cause of death.

DISCUSSION One of the most challenging problems in the field of head and neck cancer is the management and prognosis of the patient with metastatic cancer of the neck from an unknown primary. The search for the primary must be complete and should be repeated at frequent intervals. It should include examination of the oral cavity, naso-, oroand hypopharynx, larynx, esophagus, bronchial tree, external auditory canal, paranasal sinuses and nasal passages, as well as more distant sites.

Table 5. Survival after radical neck dissection

NX N,

No.

(100) (66) (40) (0)

radical neck dissection as their only treatment, especially those with few positive lymph nodes. Table 5 shows the survival of these patients according to the involved lymph nodes. All of the patients with N,, N, and N2 disease who were treated with combined surgery and radiation therapy were alive at 2 years, and 8 of 10 were alive at the completion of the study; 5 patients had survived 5 years and 3 survived less than 5 years with no evidence of disease. No patient in this group developed disease in the contralateral neck since it was treated with radiation therapy. Our results with combined surgery and radiation therapy for patients in Stage N3 are encouraging. Eighty three per cent of the patients were alive at 1 year and 1 patient survived 5 years. This is evidence of good palliation for such extensive disease. Of the 22 patients who received combined surgery and radiotherapy, 4 received preoperative radiation therapy and 18 received postoperative radiation therapy; our numbers were too small to indicate which approach is better. Follow-up of the patients showed that 6 patients

Stage

of disease

l/l 213 215 o/3

Usually a single lateral field directed to the tumor mass was used in a palliative attempt. Patients with small neck nodes were treated with

Treatment failures No. of positive nodes

Survival (months)

9724

NA 13

l/28 l/37 2184 l/30 II/23

3& 31§ 22q 368

75

only

Treatment successes No. of positive nodes

o/14 2176 O/53$ O/59$ 2176 0

Survival (yrs)t 5 11 6 5 $1,

tAlive and well with no evidence of disease at this writing. *Biopsy of involved nodes prior to radical neck dissection removed only site of disease. ORecurrence treated with radiation therapy. !/Lung primary treated. Not applicable.

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0 Physics

Usually the patient presents with a firm, painless, asymptomatic mass in the neck. In our series, 70.6% of the cases were diagnosed as epidermoid carcinoma; the rest were anaplastic carcinoma and adenocarcinoma. In other series 69% of the cases were either squamous or undifferentiated carcinoma: the next were either adenocarcinoma or miscellaneous forms.4 During the follow-up in our study, 6 of 51 patients (11.8%) eventually demonstrated a lung primary as the cause of their cervical lymph node metastases and one patient yielded an ENT primary. Other investigators reported that the primary tumor subsequently found in 25-33% of the cases.3.4*9 In almost 75% of these patients the primary tumor will never become apparent.’ Radiation therapy and surgery are not competing modalities in the treatment of patients with cervical lymphadenopathy associated with an occult primary.6 France and Lucas4 reported that 9.3% of the patients are alive and well after 2-17 years. Smith et a1.9 suggested that external radiation therapy followed by dissection of the lymph node chain for epidermoid carcinoma offers the best hope for prolonged

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1979, Volume

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survival. Jesse et a1.6 reported 48% with 3 years free of cancer. Other studies showed 13%-37% no evidence of disease rate. ‘*2*5,7*8 Our results suggest that a radical neck dissection is effective in controlling the disease in the early stages with few positive lymph nodes, i.e. in the favorable categories. In advanced categories with many positive lymph nodes, better results were obtained with combined surgery and radiation therapy. Radiation therapy could be pre- or post-operative; our numbers are too small to indicate which approach is better. In our series, follow-up of those who received a full course of radiation therapy yielded only 1 ENT primary. Apparently the aggressive irradiation has controlled these lesions and accounts for the lack of ENT primary tumor in these survivors. Jesse et a1.6 reported that 20% of patients treated with radical surgery only developed a head and neck primary while 6% of those receiving irradiation presented later with a head and neck primary. This further reinforces the policy of combined surgery and radiation treatment for better control.

REFERENCES 1. Barrie, J.R., Knapper, W.H., Strong, nodal metastases 466-470, 1970.

of unknown

E.W.: Cervical origin. Am. J. Surg. 120:

2. Comess, M.S., Beahrs, O.H., Dockerty, M.B.: Cervical metastases from occult carcinoma. Surg. Gynecol. & Obstet. 104: 607-617, 1957. 3. Fisher, D.S.: Management of cancer of unknown primary. Conn. Med. 39: 205-208, 1975. 4. France, C.J., Lucas, R.: The management and prognosis of metastatic neoplasms of the neck with an unknown primary. Am. J. Surg. 106: 835-839, 1963. 5. Jesse, R.H., Neff, L.E.: Metastatic carcinoma in cervical nodes with an unknown primary lesion. Am. J. Surg. 112: 547-553, 1966.

6. Jesse, R.H., Perez, C.A., Fletcher, G.H.: Cervical lymph node metastasis: Unknown primary cancer. Cancer 31: 854-859, 1973. 7. Marchetta, F.C., Murphy, W.T., Kovaric, J.J.: Carcinoma of the neck. Am. J. Surg. 106: 974-979, 1963. 8. Ridenhour, C.E., Yeun, P.E., Spratt, J.S., Jr.: Metastatic carcinoma in cervical lymph nodes from occult primary sites. Mod. Med. 64: 988-993, 1967. 9. Smith, P.E., Krementz, E.T., Chapman, W.: Metastatic cancer without a detectable primary site. Am. J. Surg. 113: 633-637, 1967,