Malignant Salivary Gland Tumors: Squamous Cell Carcinoma of the Submandibular Gland in a Child GERD RASP, MD, AND W. PERMANETTER,
MD
Purpose: Malignant neoplasms of the salivary glands are extremely unusual in the pediatric age group. Methods: We report an 11-year-old boy who presented with a mass in the left submandibular region and a second mass in the jugularfacial venous angle. Results: Histologic evaluation determined that this was a squamous cell carcinoma of the submandibular gland with metastasis to a cervical node. Review of the literature was undertaken to identify the rate of malignant salivary gland tumors in children. Malignant salivary gland tumors are extremely rare in children. When malignancy does occur, nearly 90% are present in the parotid gland. The submandibular gland is effected in 7.7% of cases. The most common malignancy in salivary glands of children is the mucoepidermoid carcinoma. Squamous cell carcinoma occurs in less than 2% of cases. Conclusions: Salivary gland tumors are very rare in children in contrast to adults. The proportion of malignant tumors in children is higher than that observed in adults; however, it is not possible to draw conclusions concerning treatment from the few case reports that exist. A higher rate of local recurrence and cervical lymph node metastasis may be expected in children. Copyright 0 1992 by W.B. Saunders Company
Cervical lymphadenopathy is a frequent finding in children that usually accompanies an infection of the upper respiratory tract. It is found mainly in the posterior auricular, nuchal, and submandibular regions, but above all in the jugularfacial venous angle. Enlargement of the lymph nodes is very rarely caused by neoplasms; however, this diagnosis must be considered, even in children. Only histological confirmation can provide a reliable diagnosis.‘*’ Because the most common neoplasms in children are those of the haematopoietic and lymphatic systems, such cervical lymph node enlargements can be attributed almost exclusively to these diseases. Of all the other very rare malignant tumors of the head and neck region in children, malignant tumors of the salivary glands represent
From the Klinik und Poliklinik fur Hal+, Nasen- und Ohrenkranke der Ludwig-Maximilians-Universitlt Munchen, and the Pathologisches lnstitut der LudwigMaximilians-Universitat Munchen, Germany. Address reprint requests to Gerd Rasp, MD, Assistant at the Klinik und Poliklinik fur Hals-, Nasen- und Ohrenkranke der Ludwig-Maximilians-Universitlt Munchen, Klinikum Grophadern, Marchioninistr. 15, 8000 Munchen 70, Germany. Copyright 0 1992 by W.B. Saunders Company 0196-0709/92/l 302-0007$5.00/O American
Journal
of Otolaryngology,
8%.3 Most frequently affected is the parotid gland, followed by the submandibular gland and the small salivary glands4 Between 35% and 60% of childhood salivary gland tumors are malignant.4-7 This means that a 50% greater proportion of malignant salivary gland tumors occurs in children compared with adults.* Primary squamous cell carcinomas of the salivary glands are extremely rare in adults and even more so in children. In the literature available to us, we found five cases of squamous cell carcinomas of the salivary glands in children; four of these involved the parotid gland2~g~10and one the submandibular gland.” The case reported herein is a primary squamous cell carcinoma in the region of the submandibular gland of an ll-year-old boy; regional lymph node and lung metastases developed during the course of the disease.
CASE
HISTORY
An ll-year-old boy, in good general health and nutritional status, was admitted to the hospital because of two solid tumors on the left side of the neck. On palpation, a firm, nonmovable, nontender tumor, with a radius of 2 cm, was discovered in the left submandibular region, not clearly distinguishable from the submandibular gland. A second firm
Vol 13, No 2 (March-April),
1992: pp 109-112
109
RASP AND PERMANETTER
Fig 1. Poorly differentiated, partially keratinizing squamous cell carcinoma infiltrating an atrophic salivary gland with inflammatory reaction on the left margin of the picture. (H&E; original magnification x100.) (6) Magnification of the tumor in A. Infiltration of poorly differentiated epithelium. Centrally, there is better differentiation with keratinization. (H&E, original magnification x250.1
yet still movable tumor, with a radius of approximately 2 cm was palpable in the jugularfacial venous angle. The case history did not show any evidence as to the pathogenesis of the node enlargements that had increased in size in the preceding weeks without accompanying pain. The results of an examination of the remaining ear, nose, and throat region and laboratory tests were normal. The palpable tumors were surgically extirpated under general anesthesia. During the course of the operation, a tumor originating from the submandibular gland became apparent. The tumor had already infiltrated the neighboring fatty tissue and the sublingual gland. The intraoperative histopathological examination of the excision biopsy strongly suggested the presence of an infiltrating squamous cell TABLE 1. Histopathological Histology Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Adenoid-cystic carcinoma Undifferentiated carcinoma Squamous cell carcinoma Rhabdomyosarcoma Other sarcoma Malignant lymphoma Neuroblastoma
Classification
carcinoma. The tumor of the jugularfacial venous angle, discovered during the clinical examination, proved to be a lymph node metastasis (Fig 1). A second operation, consisting of wide local excision and a neck dissection of the left side, followed histological confirmation of the diagnosis of a well-differentiated keratinizing squamous cell carcinoma by paraffin-embedded sections. No tumor mass was found in the resected material, and therefore postoperative radiotherapy was not performed. The pathological-anatomic tumor stage of the squamous cell carcinoma of the submandibular gland was designated as pT2 (pN1). The additional clinical staging tests (chest x-ray, sonogram of the upper abdomen and kidney, and total body bone scanning] showed no indication of metastasis.
and Rate of Malignant
Shikani4
Lack7
BakeP
Donath5
122
6
3
10
12
15
30
5
3
4
5
2
19
2
1
2
2
1
16
-
5
3
3
1
1
22 3
2 -
-
1
-
6-l
_--
5-3
--
3-__ 1--___
Seifert’
Salivary Gland Tumors in Children
-
__
Castro”
Dahlqvist13
Kauffman”
5 1
-
1
Jaques14
Total
%
5
19
197
51.7
3
12
64
16.8
3
31
8.1
-
1
1
-
29
7.6
2
4
-
33
8.7
-
-
1
-
5
1.3
-
1 1
-
-
-
8 9
2.1 2.4
-
3 2
0.8 0.5
-
1
MALIGNANT
TABLE 2.
SALIVARY
Localization
111
GLAND TUMORS
of Malignant
Salivary Gland Tumors in Childhood
Histology
Shikan?
Lack’
Parotid gland Submandibular gland Sublingual
190
12
13
18
15
18
17
1
2
2
3
1
gland Minor salivary glands
Bakep
Donath’
Seifeti
Castro”
2__---
1
-
5
6
Clinical follow-up examinations were performed in short intervals. Three months later, renewed tumor growth was discovered in the submental region as well as the mid-region of the neck. The tumor re-
currence was completely removed along with the neighboring muscle tissue of the submandibular region. Postoperative radiotherapy at a dose of 60 Gy was administered. The patient remained free of recurrence for 18 months. On the occasion of a routine follow-up examination, a chest x-ray detected multiple pulmonary metastases and the disease proved fatal I month later.
DISCUSSION Salivary gland tumors are very rare in children. However, in contrast to adults the proportion of malignant tumors is noticeably higher. In an overview of the literature (Table 1) on salivary gland neoplasms observed in children, mucoepidermoid carcinomas are the most common, followed by acinic cell carcinomas (16.8%), and undifferentiated carcinomas (8.7%). Adenocarcinomas (8.1%) and adenoid-cystic carcinomas (7.6%) approach the frequency of the latter. Squamous cell carcinomas, at I%, are the rarest of these very rare tumors. These malignancies involve primarily the parotid gland (88.5%) and the submandibular gland (7.7%). The small salivary glands (3 3%) and the sublingual gland (0.5%) are very rarely the origin of these tumors (Table 2). Most of these tumors appear to be radiation induced.l’ As a result of the small number of cases of malignant salivary gland tumors in children, studies concerning the rates of local recurrence and metastasis are to be regarded with caution. Among the more frequent mucoepidermoid carcinomas, relapse rates of 50% following enucleation and 30% following parotidectomy have been described.4 Cervical
-
Dahlqvist13 9
KauffmanlO
Jaquesi4
Total
%
15
34
324
88.5
-
28
7.7
-
2
-
-
-
2
0.5
-
-
-
12
3.3
lymph node metastases occur in 20% of these tumors, although a 5-year survival rate of over 96% obtained following surgical therapy with postoperative radiotherapy. Similar results are described for the acinic cell carcinoma. The prognosis is significantly poorer for the adenocarcinomas and adenoid-cystic carcinomas. Due to the extreme rarity of the squamous cell carcinoma in children, it is only possible to use isolated case reports for comparison. In one case in which a radical dissection of the submandibular region with partial resection of the mandible and a neck dissection were performed, a lymph node recurrence was reported after 2 years. This local relapse was removed and followed by radiation therapy, after which tumor-free survival was observed for another 6 years. Further developments are unknown in this case. Of the three cases of squamous cell carcinoma of the parotid gland reported in the literature, the outcome is known for only one patient, a J-year-old boy. After only 1 month, a local recurrence was observed that proved fatal 3 months later. Although it is not possible to draw conclusions concerning treatment from these few case reports, the results of therapy in mucoepidermoid carcinoma, which is most common and a part similar to the squamous cell carcinoma, do allow certain inferences. It is evident that a higher rate of local recurrence and cervical lymph node metastasis is to be expected in children compared with adults. This pattern appears to be supported by the present case.
REFERENCES 1. Gaisford WF: Malignant disease in infancy and childhood. Arch Dis Child ~1-6, 1949 2. Pack GT, LeFevre RG: The age and sex distribution and incidence of neoplastic diseases at the memorial hos-
112
pital, New York City. Cancer Res Clin Oncol 14:169-294, 1930 3. Rush BF, Chambers RG, Ravitch MM: Cancer of the head and neck in children. Surgery 53270284, 1963 4. Shikhani AH, Johns ME: Tumors of the major salivary glands in children. Head Neck 10257-263, 1988 5. Donath K, Seifert G, Lentrodt J: The embryonal carcinoma of the parotid gland. Virchows Arch [A] 403:425440,1984 6. Baker SR, Malone B: Salivary gland malignancies in children. Cancer 55:1730-1736, 1985 7. Lack EE, Upton MP: Histopathologic review of salivary gland tumors in childhood. Arch Otolaryngol Head Neck Surg 114:898-906, 1988 8. Seifert G, Okabe H, Caselitz J: Epithelial salivary gland tumors in children and adolescents. Oto-RhinoLaryngologie 48:137-149, 1986 9. Case TC: Carcinoma of the parotid gland in a youth. Ann Surg 111:155-159, 1940
RASP AND PERMANE-ITER
IO. Kauffman SL, Stout AP: Tumors of the major salivary glands in children. Cancer 16:1317-1331, 1963 11. Smith SA: Radiation-induced salivary gland tumors. Arch Otolaryngol Head Neck Surg 102:561-562, 1976 12. Castro EB, Huvos AC, Strong EW, et al: Tumors of the major salivary glands in children. Cancer 29:3I2-317, 1972 13. Dahlqvist A, Ostberg Y: Malignant salivary gland tumours in children. Acta Otolaryngol (Stockh) 94:I75179, 1982 14. Jaques DA, Krolls SO, Chambers RG: Parotid tumors in children. Am J Surg 132:469-471, 1976 15. Bianchi A, Cudmore RE: Salivary gland tumors in children. J Pediatr Surg 13:519-521, 1978 16. Krolls SO, Trodahl JN, Boyers RC: Salivary gland lesions in children. Cancer 30:459-469, 1972 17. Levine SB, Potsic WP: Acinic cell carcinoma of the parotid gland in children. Int J Pediatr Otorhinolaryngol 11:281-286, 1986
MD
Purpose: Malignant neoplasms of the salivary glands are extremely unusual in the pediatric age group. Methods: We report an 11-year-old boy who presented with a mass in the left submandibular region and a second mass in the jugularfacial venous angle. Results: Histologic evaluation determined that this was a squamous cell carcinoma of the submandibular gland with metastasis to a cervical node. Review of the literature was undertaken to identify the rate of malignant salivary gland tumors in children. Malignant salivary gland tumors are extremely rare in children. When malignancy does occur, nearly 90% are present in the parotid gland. The submandibular gland is effected in 7.7% of cases. The most common malignancy in salivary glands of children is the mucoepidermoid carcinoma. Squamous cell carcinoma occurs in less than 2% of cases. Conclusions: Salivary gland tumors are very rare in children in contrast to adults. The proportion of malignant tumors in children is higher than that observed in adults; however, it is not possible to draw conclusions concerning treatment from the few case reports that exist. A higher rate of local recurrence and cervical lymph node metastasis may be expected in children. Copyright 0 1992 by W.B. Saunders Company
Cervical lymphadenopathy is a frequent finding in children that usually accompanies an infection of the upper respiratory tract. It is found mainly in the posterior auricular, nuchal, and submandibular regions, but above all in the jugularfacial venous angle. Enlargement of the lymph nodes is very rarely caused by neoplasms; however, this diagnosis must be considered, even in children. Only histological confirmation can provide a reliable diagnosis.‘*’ Because the most common neoplasms in children are those of the haematopoietic and lymphatic systems, such cervical lymph node enlargements can be attributed almost exclusively to these diseases. Of all the other very rare malignant tumors of the head and neck region in children, malignant tumors of the salivary glands represent
From the Klinik und Poliklinik fur Hal+, Nasen- und Ohrenkranke der Ludwig-Maximilians-Universitlt Munchen, and the Pathologisches lnstitut der LudwigMaximilians-Universitat Munchen, Germany. Address reprint requests to Gerd Rasp, MD, Assistant at the Klinik und Poliklinik fur Hals-, Nasen- und Ohrenkranke der Ludwig-Maximilians-Universitlt Munchen, Klinikum Grophadern, Marchioninistr. 15, 8000 Munchen 70, Germany. Copyright 0 1992 by W.B. Saunders Company 0196-0709/92/l 302-0007$5.00/O American
Journal
of Otolaryngology,
8%.3 Most frequently affected is the parotid gland, followed by the submandibular gland and the small salivary glands4 Between 35% and 60% of childhood salivary gland tumors are malignant.4-7 This means that a 50% greater proportion of malignant salivary gland tumors occurs in children compared with adults.* Primary squamous cell carcinomas of the salivary glands are extremely rare in adults and even more so in children. In the literature available to us, we found five cases of squamous cell carcinomas of the salivary glands in children; four of these involved the parotid gland2~g~10and one the submandibular gland.” The case reported herein is a primary squamous cell carcinoma in the region of the submandibular gland of an ll-year-old boy; regional lymph node and lung metastases developed during the course of the disease.
CASE
HISTORY
An ll-year-old boy, in good general health and nutritional status, was admitted to the hospital because of two solid tumors on the left side of the neck. On palpation, a firm, nonmovable, nontender tumor, with a radius of 2 cm, was discovered in the left submandibular region, not clearly distinguishable from the submandibular gland. A second firm
Vol 13, No 2 (March-April),
1992: pp 109-112
109
RASP AND PERMANETTER
Fig 1. Poorly differentiated, partially keratinizing squamous cell carcinoma infiltrating an atrophic salivary gland with inflammatory reaction on the left margin of the picture. (H&E; original magnification x100.) (6) Magnification of the tumor in A. Infiltration of poorly differentiated epithelium. Centrally, there is better differentiation with keratinization. (H&E, original magnification x250.1
yet still movable tumor, with a radius of approximately 2 cm was palpable in the jugularfacial venous angle. The case history did not show any evidence as to the pathogenesis of the node enlargements that had increased in size in the preceding weeks without accompanying pain. The results of an examination of the remaining ear, nose, and throat region and laboratory tests were normal. The palpable tumors were surgically extirpated under general anesthesia. During the course of the operation, a tumor originating from the submandibular gland became apparent. The tumor had already infiltrated the neighboring fatty tissue and the sublingual gland. The intraoperative histopathological examination of the excision biopsy strongly suggested the presence of an infiltrating squamous cell TABLE 1. Histopathological Histology Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Adenoid-cystic carcinoma Undifferentiated carcinoma Squamous cell carcinoma Rhabdomyosarcoma Other sarcoma Malignant lymphoma Neuroblastoma
Classification
carcinoma. The tumor of the jugularfacial venous angle, discovered during the clinical examination, proved to be a lymph node metastasis (Fig 1). A second operation, consisting of wide local excision and a neck dissection of the left side, followed histological confirmation of the diagnosis of a well-differentiated keratinizing squamous cell carcinoma by paraffin-embedded sections. No tumor mass was found in the resected material, and therefore postoperative radiotherapy was not performed. The pathological-anatomic tumor stage of the squamous cell carcinoma of the submandibular gland was designated as pT2 (pN1). The additional clinical staging tests (chest x-ray, sonogram of the upper abdomen and kidney, and total body bone scanning] showed no indication of metastasis.
and Rate of Malignant
Shikani4
Lack7
BakeP
Donath5
122
6
3
10
12
15
30
5
3
4
5
2
19
2
1
2
2
1
16
-
5
3
3
1
1
22 3
2 -
-
1
-
6-l
_--
5-3
--
3-__ 1--___
Seifert’
Salivary Gland Tumors in Children
-
__
Castro”
Dahlqvist13
Kauffman”
5 1
-
1
Jaques14
Total
%
5
19
197
51.7
3
12
64
16.8
3
31
8.1
-
1
1
-
29
7.6
2
4
-
33
8.7
-
-
1
-
5
1.3
-
1 1
-
-
-
8 9
2.1 2.4
-
3 2
0.8 0.5
-
1
MALIGNANT
TABLE 2.
SALIVARY
Localization
111
GLAND TUMORS
of Malignant
Salivary Gland Tumors in Childhood
Histology
Shikan?
Lack’
Parotid gland Submandibular gland Sublingual
190
12
13
18
15
18
17
1
2
2
3
1
gland Minor salivary glands
Bakep
Donath’
Seifeti
Castro”
2__---
1
-
5
6
Clinical follow-up examinations were performed in short intervals. Three months later, renewed tumor growth was discovered in the submental region as well as the mid-region of the neck. The tumor re-
currence was completely removed along with the neighboring muscle tissue of the submandibular region. Postoperative radiotherapy at a dose of 60 Gy was administered. The patient remained free of recurrence for 18 months. On the occasion of a routine follow-up examination, a chest x-ray detected multiple pulmonary metastases and the disease proved fatal I month later.
DISCUSSION Salivary gland tumors are very rare in children. However, in contrast to adults the proportion of malignant tumors is noticeably higher. In an overview of the literature (Table 1) on salivary gland neoplasms observed in children, mucoepidermoid carcinomas are the most common, followed by acinic cell carcinomas (16.8%), and undifferentiated carcinomas (8.7%). Adenocarcinomas (8.1%) and adenoid-cystic carcinomas (7.6%) approach the frequency of the latter. Squamous cell carcinomas, at I%, are the rarest of these very rare tumors. These malignancies involve primarily the parotid gland (88.5%) and the submandibular gland (7.7%). The small salivary glands (3 3%) and the sublingual gland (0.5%) are very rarely the origin of these tumors (Table 2). Most of these tumors appear to be radiation induced.l’ As a result of the small number of cases of malignant salivary gland tumors in children, studies concerning the rates of local recurrence and metastasis are to be regarded with caution. Among the more frequent mucoepidermoid carcinomas, relapse rates of 50% following enucleation and 30% following parotidectomy have been described.4 Cervical
-
Dahlqvist13 9
KauffmanlO
Jaquesi4
Total
%
15
34
324
88.5
-
28
7.7
-
2
-
-
-
2
0.5
-
-
-
12
3.3
lymph node metastases occur in 20% of these tumors, although a 5-year survival rate of over 96% obtained following surgical therapy with postoperative radiotherapy. Similar results are described for the acinic cell carcinoma. The prognosis is significantly poorer for the adenocarcinomas and adenoid-cystic carcinomas. Due to the extreme rarity of the squamous cell carcinoma in children, it is only possible to use isolated case reports for comparison. In one case in which a radical dissection of the submandibular region with partial resection of the mandible and a neck dissection were performed, a lymph node recurrence was reported after 2 years. This local relapse was removed and followed by radiation therapy, after which tumor-free survival was observed for another 6 years. Further developments are unknown in this case. Of the three cases of squamous cell carcinoma of the parotid gland reported in the literature, the outcome is known for only one patient, a J-year-old boy. After only 1 month, a local recurrence was observed that proved fatal 3 months later. Although it is not possible to draw conclusions concerning treatment from these few case reports, the results of therapy in mucoepidermoid carcinoma, which is most common and a part similar to the squamous cell carcinoma, do allow certain inferences. It is evident that a higher rate of local recurrence and cervical lymph node metastasis is to be expected in children compared with adults. This pattern appears to be supported by the present case.
REFERENCES 1. Gaisford WF: Malignant disease in infancy and childhood. Arch Dis Child ~1-6, 1949 2. Pack GT, LeFevre RG: The age and sex distribution and incidence of neoplastic diseases at the memorial hos-
112
pital, New York City. Cancer Res Clin Oncol 14:169-294, 1930 3. Rush BF, Chambers RG, Ravitch MM: Cancer of the head and neck in children. Surgery 53270284, 1963 4. Shikhani AH, Johns ME: Tumors of the major salivary glands in children. Head Neck 10257-263, 1988 5. Donath K, Seifert G, Lentrodt J: The embryonal carcinoma of the parotid gland. Virchows Arch [A] 403:425440,1984 6. Baker SR, Malone B: Salivary gland malignancies in children. Cancer 55:1730-1736, 1985 7. Lack EE, Upton MP: Histopathologic review of salivary gland tumors in childhood. Arch Otolaryngol Head Neck Surg 114:898-906, 1988 8. Seifert G, Okabe H, Caselitz J: Epithelial salivary gland tumors in children and adolescents. Oto-RhinoLaryngologie 48:137-149, 1986 9. Case TC: Carcinoma of the parotid gland in a youth. Ann Surg 111:155-159, 1940
RASP AND PERMANE-ITER
IO. Kauffman SL, Stout AP: Tumors of the major salivary glands in children. Cancer 16:1317-1331, 1963 11. Smith SA: Radiation-induced salivary gland tumors. Arch Otolaryngol Head Neck Surg 102:561-562, 1976 12. Castro EB, Huvos AC, Strong EW, et al: Tumors of the major salivary glands in children. Cancer 29:3I2-317, 1972 13. Dahlqvist A, Ostberg Y: Malignant salivary gland tumours in children. Acta Otolaryngol (Stockh) 94:I75179, 1982 14. Jaques DA, Krolls SO, Chambers RG: Parotid tumors in children. Am J Surg 132:469-471, 1976 15. Bianchi A, Cudmore RE: Salivary gland tumors in children. J Pediatr Surg 13:519-521, 1978 16. Krolls SO, Trodahl JN, Boyers RC: Salivary gland lesions in children. Cancer 30:459-469, 1972 17. Levine SB, Potsic WP: Acinic cell carcinoma of the parotid gland in children. Int J Pediatr Otorhinolaryngol 11:281-286, 1986
