malignant lymphoepithelial lesion of the submandibular gland

Malignant lymphoepithelial lesion of the submandibular gland Ana Lucia iU. P. Amaral, M.D., and Antonio G. Nascimento, M.D., Rio de Janeiro, Brazil

DEPARTMENT OF ANATOMIC PATHOLOGY, NATIONAL INSTITUTE OF CANCER

A case of malignant lymphoepithelial lesion of the submandibular gland is reported and the literature

is reviewed. This neoplasm has been described frequently in Eskimos and is usualty located in the

parotid gland. The histogenesis of the lesion is discussed. The tumor shows local aggressiveness,

with frequent recurrences and metastases to regional lymph nodes. Surgical treatment consisting of

wide resection of the tumor with regional lymph node dissection, with or without radiotherapy, seems

to be the most appropriate therapy.

(ORAL SURG. 58:184-190, 1984)

I n 1952 Godwin’ introduced the term benign lymphoepithelial lesion (BLEL) to designate several cases reported in the literature with different names but showing a similar histologic picture (that is, the presence of epithelial and lymphoid elements in variable proportion). The author did not speculate as to whether the lesion was neoplastic or inflammatory but called attention to a possible malignant potential, whether epithelial or lymphoid.

In 1962 Hilderman and co-workers* described the first case of what appeared to be the malignant counterpart of the BLEL. This lesion, which origi- nated in the parotid gland, was called malignant lymphoepithelial lesion (MLEL).

Since that time, thirty-one cases of MLEL have been described in the English-language literature. The case that will be described in this paper is the thirty-second case but only the second one reported in the submandibular gland.

CASEREPORT

An 86-year-old white woman sought medical care in April, 1981, complaining of a mass of 5 months duration in the left submandibular region. The tumor was nontender and showed slow but progressive growth, ulcerating the skin and exuding a whitish material.

Physical examination showed an ulcerated and mobile nodule, measuring 4 cm in diameter, in the left submandibular region. A lymph node, which was mobile and firm and measured 0.5 cm, was present in the left supraclavicu- lar region. An evaluation of nasopharynx and lungs at that time was negative.

In July, 198 1, the submandibular gland, adjacent lymph nodes, and the overlying skin were resected en bloc. The

184

postoperative course was unremarkable, and radiotherapy was offered. However, the patient refused any adjuvant treatment. The last information about the patient was obtained in October, 1983, at which time she was well with no evidence of disease.

Pathologic findings

The surgical specimen consisted of a segment of skin and soft tissues showing a large, ulcerated, vegetant lesion measuring 5.0 x 4.5 cm. The cut section had a yellowish, firm, lobulated surface.

Histologically, the neoplasm was composed of oval and spindle cells showing pleomorphic, vacuolated nuclei with prominent nucleoli and high mitotic activity. The cells formed nests lying in an abundant lymphoid stroma, consisting of typical lymphocytes (Figs. 1, 2, and 3). The tumor invaded soft tissues adjacent to the submandibular gland and involved the skin, producing necrosis and ulcer- ation. In some areas benign epithelial nests lying in a dense lymphoid stroma were seen (Fig. 4). The tumor involved most of the submandibular gland, with uninvolved glandu- lar tissue exhibiting atrophy with fibrosis and marked chronic inflammation.

Within the gland were dilated ducts showing a double layer of flat, cuboidal epithelial cells. In one of these ducts there was a transition from benign ductal epithelium to the neoplastic process, passing through an intermediate histologic stage of atypical cellular proliferation.

The lymph nodes showed a histologically similar metastatic tumor (Fig. 5).

REVIEW OF THE LITERATURE

Thirty-one cases of MLEL have been reported thus far in the English-language literature (Ta- ble I).

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Malignant lymphoepithelial lesion of submandibular gland 185

Fig. 1. Malignant lymphoepithelial lesion. Note malignant epimyoepithelial island lying in a lymphoid stroma. (Hematoxylin and eosin stain. Magnification, X40.)

Fig. 2. Malignant lymphoepithelial lesion with malignant epimyoepithelial islands lying in a stroma of typicai lymphocytes. The epithelial nests are composed of pleomorphic cells showing spindle or oval nuclei and basophilic cytoplasm with indistinct horders. Note mitotic activity (Hematoxylin and eosin stain. Magnification, x400.)

166 Amaral and Nascimento Oral Surg. August, 1984

Fig. 3. For legend, see Fig. 2.

The lesion shows a slight preference for females (eighteen patients). The ages of the patients ranged between 17 and 66 years, with a median age of 41.5 years. Thirteen patients were in the fourth decade of life.

The race of the patients was known in twenty- seven cases; there were fifteen Eskimo, six white, two black, two Indian, and two Oriental patients.

Twenty-nine tumors were located in the parotid gland and one in the submandibular gland. In one case the location of the lesion was unknown. The tumor involved a single gland in all reported cases.

There was information about treatment in thirty cases; surgical procedures were performed in twenty- eight, and in seven cases radiotherapy was also given. In twenty-three cases surgery was radical; in thirteen of these regional lymph node dissection was also done. Five cases were treated only by excision of the tumor. Radiotherapy only was used in one case. Adjuvant chemotherapy was used in two cases. The last case was not treated.

In twenty-two cases the malignant epithelial component was diagnosed as undifferentiated carcinoma. Poorly differentiated epidermoid carcinoma and adenocarcinoma were diagnosed in three other instances. In four cases the diagnosis was carcinoma, not otherwise specified, and there was no information about the histologic type of the malignant process in two cases. In cases 1, 11, 24, 25, and 29 residual areas of BLEL were identified. In Cases 9 and 19 granulomas were present, but only Case 9 showed necrosis.

Local recurrence occurred in eleven cases and metastases in eighteen. In eight cases there was no recurrence or metastasis and in four cases there was no follow-up. All eighteen patients who developed metastases in the course of the disease had irivoke- ment of the cervical lymph nodes; only seven patients developed distant metastases. Distant lymph nodes and lungs were the organs most frequently involved, each being the site of metastasis in four instances.

The period of follow-up in twenty-six patients

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Fig. 4. Benign area showing epimyoepithelial nests composed of typical cells lying in a dense lymphoid stroma. (Hematoxylin and eosin stain. Magnification, x400.)

Fig. 5. Malignant lymphoepithelial lesion metastatic to cervical lymph node. Histologically identical to the primary lesion. (Hematoxylin and eosin stain. Magnification, x400.)

188 Amaral and Nascimento Oral Surg. August, 1984

Table I. Reported cases of malignant lymphoethelial lesion

___?_- Recurrence Author Age Histologic and/or FOllOW-Up

Case and year Sex (Yr) Race Localization Treatment we metastasis [mo.) -

01 Hilderman et

aly2 1962

02 Wallace et al.,’ 1963

03 Wallace et al., 1963

04 Wallace et a1.,5 1963

05 Wallace et al.,5

1963 06 Wallace et al.,’

I963 07 Wallace et al.,s

1963 08 Wallace et al.,3

1963 09 Wallace et al.,’

1963 IO Wallace et al.,s

1963 I I Delaney and

Balogh: 1966

I2 Gravanis and Giansanti,’

1970

I3 Gravanis and Giansanti,’

1970 14 Gravanis and

Giansanti,’ 1970

M 40

F 43

F 23

M 38

M 36

F 43

M 35

M 17

M 49

M 29

F 66

M 54

F 39

F 80 Black

White

Eskimo

Eskimo

Eskimo

Eskimo

Eskimo

Eskimo

Eskimo

Eskimo

Eskimo

White

Black

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Parotid

Key to abbreviations: PDEC * Poorly ditkrentiated epidermoid carcinoma; UC * unditkrentiated carcinoma; FDA = pearly differentiated adenocarcinoma; CNOS = carcinoma not otherwise specified; R = recurrence; Me = metastasis; DoD = dead of disease; AWD = alive with disease; AW = alive and well;

DUC = dead of unrelated causes

varied from 4 to 108 months, and in five reports this information was not obtained. Five patients (Cases 1, 2,3,4, and 5) died of the disease 60,9, 24, 14, and 6 months after diagnosis, respectively. Two patients died of unrelated causes, 108 and 13 months after the diagnosis, apparently with no evidence of disease. Five patients were alive with disease at 4, 12, 16, 14, and 20 months. The other fourteen patients were alive without evidence of tumor from 8 to 108 months after diagnosis.

DISCUSSION

The relationship between the MLEL and its benign counterpart has not been completely estab- lished until now. Facts that indicate a relationship between the two entities are the presence of benign and malignant areas in a given tumor and/or the evolution in certain cases of lesions that initially appear histologically as BLEL and after recurrence3

Surgery

Surgery

Surgery + radiotherapy


Radiotherapy

Surgery


None



Surgery

Surgery

Surgery

Surgery

PDEC

UC

UC

UC

UC

UC

UC

UC

UC

UC

PDA

UC

UC

CNOS

R, Me

R, Me

Me

R, Me

R, Me

Me

R, Me

Me

Me

R, Me

R, Me

R, Me

-

DOD; 60

DOD; 9

DOD; 24

DOD; 14

DOD; 6

AWD; 4

AWD; 12

AW; 66

AW; 84

AWD; 16

DUC; 108

AW; 42

AW; 38

are characterized as malignant. On the other hand, the presence of numerous cases in which the malignant process appears to arise de novo suggests that these two entities are not pathogenetically related. This last hypothesis is re-emphasized hy the rarity of the association between MLEL and Sjbgren’s syndrome (reported in only one of the thirty-two cases of the entity). The association of Sjiigren’s syndrome with BLEL is frequent.

Accordingly, Ferlito and Cattai3w4 believe that the MLEL, even when initially diagnosed as BLEL, represents an incipient stage of anaplastic carcinoma of ductal origin and not a consequence of the evolution of the benign process4

In our opinion, the type of carcinoma present in the MLEL must be specified. For example, our case would be called malignant lymphoepitheliai lesion with a component of undiierentiated carcinoma.

In this article we report the case of an 86-year-old

Volume 58 Number 2


Table I. Cont’d

Case Author

and year Age

Sex (Yr) Race Localization Treatment

Recurrence

Histologic and/or Follow-up

we metastasis ho.1

15 16

17 18 19

20

21 22

23

Arthaud: 1972

Arthaud,8 1972 Arthaud,8 1972

Arthaud: 1972 Arthaud,8 1972

Arthaudt 1972 Arthaud,8 1972

Arthaud,B 1972

Schnitzer and Weaver:

1974 Batsakis et al.,”

1975 Ferlito and

Donati,” 1977

Ferlito and Donati,”

1977 Ferlito and

Donati,” 1977

Roncevic and Tatic,12 198 1

Redondo et

al.,13 1981 Nagao et a1.,14

1983 Nagao et al.,”

1983 Present case

F 30 F 52

F 39 M 47

F 49 M 26

F 32 F 34 - -

Indian Eskimo

Eskimo Eskimo

Eskimo Eskimo

Indian Eskimo

-

Parotid

Parotid

Parotid Parotid

Parotid Parotid

Parotid Parotid

Surgery Surgery

Surgery Surgery

Surgery Surgery

Surgery Surgery

-

UC Me

UC -

UC -

UC R, Me

UC R UC Me

UC -

UC - - -

AW; 8 AW; 19

AW; 12 DUC; 13

AW; 108 AWD; 14

-

-

-

UC R, Me

CNOS Me

AW; 62

AW; 36

CNOS AW; 36

CNOS AW; 12

Not stated

PDEC Me

UC

UC

UC Me

AWD; 20

AW; 21

AW; 17

AW; 28

Submandibular

gland

Parotid

Surgery 24 M 50 White

25 F 36 White Surgery

26 F 55 White Parotid Surgery

27 F 32 White Parotid Surgery

28 F 38 - Parotid Surgery + radiotherapy

M 35 - Parotid Surgery 29

30 F 34 Oriental Parotid Surgery + radiotherapy +

chemotherapy Surgery + chemotherapy F 46 Oriental Parotid 31

32 F 86 White Submandibular Surgery

white woman, the oldest patient reported to date. This case is also unusual in that it involved the submandibular gland.

The malignant component of the case studied by us is of epithelial nature corresponding to an undifferentiated carcinoma. There was not any alteration in the histology, of the lymphoid component. Twen- ty-two of the twenty-nine reported cases in the literature in which there was information about the type of carcinoma were classified as undifferentiated carcinoma. A common characteristic of the tumor observed in our case as well as in the majority of the reported ones is its local aggressiveness as repre- sented by the extension into adjacent soft tissues and involvement of the facial nerve. In our case the lesion involved and ulcerated the skin. These facts are probably responsible for the great frequency of local recurrence of the tumor.

In our case, as well as in other eighteen previously published cases, there was regional lymph node

metastasis. Despite this feature, only seven patients developed distant metastases and fifteen patients, including ours, were alive with no evidence of disease at the end of the follow-up period. (Six of these patients showed regional lymph node metastases, and one of them underwent a thoracotomy for treatment of a pulmonary metastasis.)

On the basis of these observations, it is our opinion that the optimal treatment of the MLEL is wide resection of the lesion with examination of the surgical borders, accompanied by cervical lymph node dissection. Radiotherapy must be used in cases where complete resection of the tumor was not achieved.

REFERENCES

1. Godwin JT: Benign lymphoepithelial lesion of the parotid gland: report of eleven cases. Cancer 5: 1089-l 103, 1952.

2. Hilderman WC. Gordon JS, Large HL Jr, Carrol CF Jr:

Malignant lymphoepithelial lesion with carcinomatous component apparently arising in parotid gland: a malignant

190 Amaral and Nascimento Oral Surg. August, 19x4

3.

4.

5.

6.

I.

8.

9.

IO.

counterpart of benign lymphoepithelial lesion? Cancer 1% 606-610, 1962. Ferlito A, Cattai N: The so-called “benign lymphoepithelial lesion” (Part 1. Explanation of the term and of its synonymous and related terms). J Laryngol Otol 94: 1189-l 197, 1980. Ferlito A, Cattai N: The so-called “benign lymphoepithelial lesion” (Part II. Clinical and pathological considerations with regard to evolution). J Laryngol Otol 94: 1283-l 301, 1980. Wallace AC, MacDougall JT, Hildes JA, Lederman JM: Salivary gland tumours in Canadian eskimos. Cancer 16: 1338-1353, 1963. Delaney WE, Balogh K Jr: Carcinoma of the parotid gland associated with benign lymphoepithelial lesion (Mikulicz’s disease) in Sjiigren’s syndrome. Cancer 19: 853-860, 1966. Gravanis MB, Giansanti JS: Malignant histopathologic counterpart of the benign lymphoepithelial lesion. Cancer 26: 1332-1342, 1970. Arthaud JB: Anaplastic parotid carcinoma (“Malignant lymphoepithelial lesion”) in seven Alaskan natives. Am J Clin Pathol 57: 275-286, 1972. Schnitzer B, Weaver DK: In Batsakis JG: Tumours of the head and neck: clinical and pathological considerations, ed. I, Baltimore, 1974, Williams & Wilkins Company, p. 367. Batsakis JG, Bernacki EC, Rice DH, Stebler ME: Malignan- cy and the benign lymphoepithelial lesion. Laryngoscope 85: 389-399, 1975.

I 1. Ferlito A, Donati LF: “Malignant lymphoepithelial lesions” (undifferentiated ductal carcinomas of the parotid gland): three case reports and review of the literature. .I Laryngol Otol 91: 869-885, 1977.

12. Roncevic R, Tatic V: Malignant lympoepithelial leston: report of case. J Oral Surg 39: 449-450, I98 1.

13. Redondo C, Garcia A, Vazquez F: Malignant lymphoepithelial lesion of the parotid gland: poorly differentiated squa- mous cell carcinoma with lymphoid stroma. Cancer 48: 289-292, 1981.

14. Nagao K, Matsuzaki 0, Saiga H, Akikusa B, Sugano I, Shigematsu H, Kaneko T, Katoh T. Kitamura T, Asano Y, Okamoto M: A histopathological study of benign and malignant lymphoepithelial lesions of the parotid gland. Cancer 52: 1044-1052, 1983.

Reprint requests to.

Dr. Ana Lucia M. P. Amaral Department of Anatomic Pathology National Institute of Cancer Praqa Cruz Vermelha, 23 Rio de Janeiro, 20230, Brazil

malignant lymphoepithelial lesion of the submandibular gland

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