Short communications
& case reports
Primary malignant melanoma in the parotid gland Mordechay Bahar, MD,a Yakir Anavi, DMD,b Aristide Abraham, MD,a and Mina Ben-Bassat, MD,c Petah Tiqva, Israel BEILINSON MEDICAL CENTER, SACKLER FACULTY OF MEDICINE, TEL AVIV UNIVERSITY Reports of primary malignant melanoma arising from the parotid salivary gland are extremely rare and, to date, have been sporadic. We report a pertinent case, and tabulate and correlate the clinical findings of the 13 cases reported thus far in the literature. The most common symptom is a progressively enlarging, asymptomatic, firm, and fixed mass. Total excision has been the established treatment of choice. The contribution of radiotherapy, chemotherapy, and immunotherapy remains unclear, and it is not possible at present to predict the outcome of treatment in individual patients. Although rare, primary malignant melanoma should be considered in the differential diagnosis of parotid tumors. The clinical significance of establishing the diagnosis of primary malignant melanoma of the parotid gland is emphasized.
(ORALSURC ORAL.MEDORALPATHOL~~~~;~~:~~~-~O)
T
he incidence of primary malignant melanoma in the head and neck area is high and accounts for about 20% of all melanomas.‘~2 Cutaneous melanomas of this region are common, whereas the incidence of mucosal melanomas is much lower.* Primary malignant melanoma of the parotid gland is extremely rare, and the current knowledge is basedon anecdotal case reports3-I0 The following case describes primary malignant melanoma of the parotid gland in a 28-year-old woman; the clinical aspects of previously reported casesare reviewed. CASEREPORT
In September1984 a 28-year-old woman was seenat the ear, noseand throat clinic with a painless left parotid lump, enlarging progressively during the past 6 months. There was aDepartment of Otolaryngology-Head and Neck Surgery. bDepartment of Oral and Maxillofacial Surgery. CDepartment of Pathology. 7/14/20679
no other significant finding in her medical history except for low blood pressure. Physical examination disclosed a fit woman in no acute distress. A left preauricular nontender, expansile mass measuring 3 X 2 cm could be palpated. The masswas firm, noncompressible,and fixated to the underlying soft tissues. The overlying skin was normal, and there was no thrill or bruit. Clear saliva flowed from the duct, and there was no facial weakness,trismus, or lymphadenopathy. Results of further head and neck and whole body examinations were unremarkable. Comprehensiveradiographic examination including computed tomographic scan of the head and neck revealed a homogenousdensity in the left parotid region without bony involvement and that did not extend into the infratemporal or pterygomaxillary spaces.Routine chest radiographs and computed tomographic scans of the thorax and abdomen failed to suggestevidenceof metastatic disease.Laboratory studies, which included complete blood cell count, electrolytes, automated chemistry panel @MA 12), and urinalysis, were within normal limits. Fine-needle aspiration from the mass was interpreted as possibly “low-grade fibrosar-’ coma.” On surgical exploration and elevation of the subcutane627
628
Bahar et al.
Fig. 1. Representative area of tumor showing melanoma cells densely packed in sheets. (Hematoxylin-eosin stain; original magnification, X40.)
ORAL SURC ORAL
MED ORAL PATHOI November 1990
ular borders and was predominantly solid with areas of necrosis. The specimen contained two parotid gland lymph nodes, both grossly and microscopically free of neoplasm. The paraffin sections of the specimen revealed that the entire parotid gland was diffusely infiltrated and mostly replaced by the neoplastic tissue. The tumor was composed of sheets of large spindle cells, which were rather uniform with elongated nuclei and had moderately prominent nucleoli (Fig. I). Moderate pleomorphism and scattered mitotic figures were identified. Fine brown granulations, which disappeared after bleaching, were prominent in the cytoplasm of the tumor cells. The neoplastic cells showed characteristics of melanocytes reacting positively for S- 100 protein and Fontana-Masson stain. Unfortunately, fresh material was not available and dopa reaction was not performed. Remnants of salivary gland tissue were identified within the tumor (Fig. 2). The histologic findings were consistent with a diagnosis of malignant melanoma. The melanoma cells extended to the excised muscle. DISCUSSION
Fig. 2. Diffuse infiltration of parotid gland by melanoma cells, replacing salivary gland tissue. Only a few acini and a small duct are present in this area. (Hematoxylin-eosin stain; original magnification, X 100.)
ous soft tissues, a brown-black, firm tumor mass infiltrated the parotid gland and the facial nerve diffusely and extended to the auricular cartilage and masseter muscle. Definitive surgical care included a left total parotidectomy with the contiguous soft tissues. Intraoperative frozensection examination indicated all clinically questionable margins to be free of neoplasm. Six weeks after surgery the patient began a course of nonspecific immunologic stimulation with bacille CalmetteGuerin treatments for a period of 2 months. The patient is well 4 years after surgery, with no evidence of tumor spread into a surrounding compartment or of metastases. The surgical specimen, measuring 6 X 3 X 3 cm, consisted of the parotid gland and the neighboring soft tissues. On cut section a dark brown tumor mass was seen occupying almost the entire parotid gland. The tumor had irreg-
The most common instances of malignant melanoma in the parotid gland are metastasesfrom other regions.’ I, l2 Reports of primary malignant melanoma of the parotid gland are scarce. The earliest report was by Remy13in 1875; his report and others are not included in the present review on the basis of either being actually metastatic tumors from another primary site within the parotid gland, or lacking adequate information. A search of the available literature yielded only 13 documented cases,3-‘oand the clinical features are summarized in Table I. Primary malignant melanoma of the parotid gland arises from melanocytes present in the normal tissue of this organ. This was demonstrated by Greene and Bernier,6 studying normal human parotid gland tissue stained by the dopa method. These authors suggested two criteria for ruling out the possibility of metastatic melanoma in the parotid gland: (1) histopathologic demonstration of malignant melanoma in the parotid gland and (2) inability to demonstrate any other primary origin of the tumor. In the present case these criteria were demonstrated. The diagnosis of malignant melanoma was established by histochemical and immunohistochemical examination, which gave positive results for melanoma cells. Dopa reaction was not performed, becausethe material was fixed in formalin. No further evidence of disease in any other body sites was disclosed after detailed clinical investigation. Greene and Bernie&’ also emphasized that metastatic lesions appear either in parotid lymph nodes or as well-delineated lesions in the parotid gland, whereas the primary tumor is infiltrative and poorly demarcated or completely replacing the pa-
Primary malignant melanoma of parotid gland
Volume 70 Number 5
Table
629
I. Cases in the literature of primary malignant melanoma of the parotid gland Age (yr)/sex
Author (yr)
Clinical presentation
Treatment
Metastases
Follow-up
Migneco ( 1934)4
65/M 62/M 77/M
Jorgensen ( 1954)s
77/M
PM PM PM, firm, fixed PM
Greene and Bernier (1961)6
67/M
PM
P RT Excision
28/M
PM
P
Widespread in body
41/M 66/F 63/F
PM PM, firm PM, firm, fixed PM
P P Enucleation
None None None
R, 7 and 18 mo; DOD, 3.5 yr R, 2 mo; DOD, 4 yr NED, 4 yr NED, 3 yr
Enucleation, RT P, neck dissection, RT (100 Gy), chemotherapy, BCG immunotherapy P, RT (105 Gy) P, RT (48 Gy) P, BCG immunotherapy
CLN
Not reported
CLN, 1 yr; lungs, 3 yr
R, 1 and 1.5 and 3 yr; DOD, 3 yr
None Lung, 8 mo None
NED, 10 mo DOD, 8 mo NED, 4 yr
Delaini (1910)3
Marchegiani
( 1963)7
Cirri and Anderetta (1967)s Brocheriou et al. (1978)9
Konevalov (1978)‘O Our case BCG. Bacille Calmette-G∈ currence; RT, radiotherapy.
72/F 22/M
PM, firm, fixed
47/F 65/M 28/F
PM, firm PM, soft PM, firm, fixed
Excision Excision P
None None Lung
Died, 7 mo from ileus R, 2 mo; DOD, 4 mo; DOD, 6 mo
CLN
Died, 7 wk from MI
Cerebral
DOD, 1 yr
CLN, cervical lymph nodes; DOD, died of disease;NED, no evidence of disease;P. parotidectomy; PM. parotid mass;R, re-
rotid gland. This description parallels the gross and microscopic features in our case. In all the reviewed casesthe main clinical presentation was a progressively enlarging asymptomatic massin the area of the parotid gland, usually firm and fixed by skin and/or deep structures. Only one of the patients displayed initially persistent facial nerve paralysis. Metastases, regional or distant, developed in sevenpatients: three in the regional cervical nodesand four in other body sites, with the lungs being most frequently involved. Surgery, radiation therapy, chemotherapy, and immunotherapy, alone or in combination, were employed in the treatment protocols for the casesin the literature. All 14 patients were treated surgically with procedures varying from wide local excision to total parotidectomy. Four patients had local recurrences. Unless the patient has metastatic melanoma, radical surgery is the initial treatment of choice. However, primary excision is likely to be inadequate becauseof the site of the tumor and the fact that melanoma often extends beyond the visible lesion. It is important to perform frozen sections to verify the adequacy of the surgical margins and to study the entire primary
lesion by subserial section analysis. This may help to preclude sampling error and thereby reduce the rate of recurrence and metastasis. The question whether prophylactic lymph node dissection is of great value is still controversial.14-‘6 Six patients received adjuvant therapy. The benefit of radiotherapy, chemotherapy, and immunotherapy is limited and unclear, becausethe effect on the six patients described indicates no consistent relationship between the type or complexity of therapy and survival rate. The recognition of primary malignant melanoma of the parotid gland has great clinical significance, because a primary lesion is amenable to appropriate surgical treatment, whereas a metastatic lesion cannot be treated successfully and is always fatal. Follow-up information was available on 11 patients; period of survival ranged from 6 months to 4 years, with a mean of 2.3 years. Five patients are alive and free of disease 10 months to 4 years after treatment. Of the four patients known to have died of their disease,period of survival ranged from 8 months to 3% years. The premature death of two patients precludes survival analysis of these cases.In general, the length of follow-up in these 11 caseshas beentoo short
630 Bahar et al. to determine any reliable conclusions as to the effectiveness of various modalities of treatment; however, total excision remains the treatment of choice.
ORAL SURG ORAL MED ORAL PATHOL November 1990
10. 11.
REFERENCES 1. Conley J, Hamaker RC. Melanoma of the head and neck. Laryngoscope 1977;87:460-4. 2. Batakis JG. Tumors of the head and neck. 2nd ed. Baltimore: Williams & Wilkins, 1982:431-47. 3. Delaini F. Di due sarcomi melanotici primitivi della parotide. Rif Med 1910;26:792-6. 4. Migneco A. Sul melanoma della parotide. Arch Ital Chir 1934;36:670-6. 5. Jorgensen MB. Malignant melanoma of the parotid gland. Am J Surg 1954;87:275-7. 6. Greene GW, Bernier JL. Primary malignant melanomas of the parotid gland. Oral Surg 1961;14:108-16. 7. Marchegiani C. In tema di tumori rari delle ghiandole salivari: il melanoma della parotide. Ann Ital Chir 1963;47:1099-111. 8. Cirri GP, Andretta 0. Infrequent tumors of the parotid gland. Arch Ital Path01 Clin 1967;10:397-425. 9. Brocheriou C, Vaillant JM, Szpirglas H, et al. Melanome ma-
12. 13. 14.
15. 16.
lin primitif de la parotide: une observation. Rev Stomatol Chir Maxillofac 1978;79:61-8. Konevalov RV. Melanoma of the parotid salivary gland. Vestn Khir 1978;108:118-9. Conley J, Arena S. Parotid gland as a focus of metastasis. Arch Surg 1963;87:757-64. Nichols RD, Pinnock LA, Szymanowski RT. Metastases to parotid nodes. Laryngoscope 1980;90:1324-8. Remy RA. Tumeur de la parotide. Bull Sot Anat Paris 1875. Ames FC, Sugarbaker EV, Ballantyne AJ. Analysis of surgical and disease control in stage I melanoma of the head and neck. Am J Surg 1976;132:484-91. Olson RM, Woods JE, Soule EH. Regional lymph node management and outcome in 100 patients with head and neck melanoma. Am J Surg 1981;142:470-3. Snow GB, van der Waal I. Mucosal melanomas of the head and neck. Otolaryngol Clin North Am 1986;19:537-47.
Reprint requests to: Dr. M. Bahar Department of Otolaryngology-Head Beilinson Medical Center Petah Tiqva, 49 100, Israel
and Neck Surgery
& case reports
Primary malignant melanoma in the parotid gland Mordechay Bahar, MD,a Yakir Anavi, DMD,b Aristide Abraham, MD,a and Mina Ben-Bassat, MD,c Petah Tiqva, Israel BEILINSON MEDICAL CENTER, SACKLER FACULTY OF MEDICINE, TEL AVIV UNIVERSITY Reports of primary malignant melanoma arising from the parotid salivary gland are extremely rare and, to date, have been sporadic. We report a pertinent case, and tabulate and correlate the clinical findings of the 13 cases reported thus far in the literature. The most common symptom is a progressively enlarging, asymptomatic, firm, and fixed mass. Total excision has been the established treatment of choice. The contribution of radiotherapy, chemotherapy, and immunotherapy remains unclear, and it is not possible at present to predict the outcome of treatment in individual patients. Although rare, primary malignant melanoma should be considered in the differential diagnosis of parotid tumors. The clinical significance of establishing the diagnosis of primary malignant melanoma of the parotid gland is emphasized.
(ORALSURC ORAL.MEDORALPATHOL~~~~;~~:~~~-~O)
T
he incidence of primary malignant melanoma in the head and neck area is high and accounts for about 20% of all melanomas.‘~2 Cutaneous melanomas of this region are common, whereas the incidence of mucosal melanomas is much lower.* Primary malignant melanoma of the parotid gland is extremely rare, and the current knowledge is basedon anecdotal case reports3-I0 The following case describes primary malignant melanoma of the parotid gland in a 28-year-old woman; the clinical aspects of previously reported casesare reviewed. CASEREPORT
In September1984 a 28-year-old woman was seenat the ear, noseand throat clinic with a painless left parotid lump, enlarging progressively during the past 6 months. There was aDepartment of Otolaryngology-Head and Neck Surgery. bDepartment of Oral and Maxillofacial Surgery. CDepartment of Pathology. 7/14/20679
no other significant finding in her medical history except for low blood pressure. Physical examination disclosed a fit woman in no acute distress. A left preauricular nontender, expansile mass measuring 3 X 2 cm could be palpated. The masswas firm, noncompressible,and fixated to the underlying soft tissues. The overlying skin was normal, and there was no thrill or bruit. Clear saliva flowed from the duct, and there was no facial weakness,trismus, or lymphadenopathy. Results of further head and neck and whole body examinations were unremarkable. Comprehensiveradiographic examination including computed tomographic scan of the head and neck revealed a homogenousdensity in the left parotid region without bony involvement and that did not extend into the infratemporal or pterygomaxillary spaces.Routine chest radiographs and computed tomographic scans of the thorax and abdomen failed to suggestevidenceof metastatic disease.Laboratory studies, which included complete blood cell count, electrolytes, automated chemistry panel @MA 12), and urinalysis, were within normal limits. Fine-needle aspiration from the mass was interpreted as possibly “low-grade fibrosar-’ coma.” On surgical exploration and elevation of the subcutane627
628
Bahar et al.
Fig. 1. Representative area of tumor showing melanoma cells densely packed in sheets. (Hematoxylin-eosin stain; original magnification, X40.)
ORAL SURC ORAL
MED ORAL PATHOI November 1990
ular borders and was predominantly solid with areas of necrosis. The specimen contained two parotid gland lymph nodes, both grossly and microscopically free of neoplasm. The paraffin sections of the specimen revealed that the entire parotid gland was diffusely infiltrated and mostly replaced by the neoplastic tissue. The tumor was composed of sheets of large spindle cells, which were rather uniform with elongated nuclei and had moderately prominent nucleoli (Fig. I). Moderate pleomorphism and scattered mitotic figures were identified. Fine brown granulations, which disappeared after bleaching, were prominent in the cytoplasm of the tumor cells. The neoplastic cells showed characteristics of melanocytes reacting positively for S- 100 protein and Fontana-Masson stain. Unfortunately, fresh material was not available and dopa reaction was not performed. Remnants of salivary gland tissue were identified within the tumor (Fig. 2). The histologic findings were consistent with a diagnosis of malignant melanoma. The melanoma cells extended to the excised muscle. DISCUSSION
Fig. 2. Diffuse infiltration of parotid gland by melanoma cells, replacing salivary gland tissue. Only a few acini and a small duct are present in this area. (Hematoxylin-eosin stain; original magnification, X 100.)
ous soft tissues, a brown-black, firm tumor mass infiltrated the parotid gland and the facial nerve diffusely and extended to the auricular cartilage and masseter muscle. Definitive surgical care included a left total parotidectomy with the contiguous soft tissues. Intraoperative frozensection examination indicated all clinically questionable margins to be free of neoplasm. Six weeks after surgery the patient began a course of nonspecific immunologic stimulation with bacille CalmetteGuerin treatments for a period of 2 months. The patient is well 4 years after surgery, with no evidence of tumor spread into a surrounding compartment or of metastases. The surgical specimen, measuring 6 X 3 X 3 cm, consisted of the parotid gland and the neighboring soft tissues. On cut section a dark brown tumor mass was seen occupying almost the entire parotid gland. The tumor had irreg-
The most common instances of malignant melanoma in the parotid gland are metastasesfrom other regions.’ I, l2 Reports of primary malignant melanoma of the parotid gland are scarce. The earliest report was by Remy13in 1875; his report and others are not included in the present review on the basis of either being actually metastatic tumors from another primary site within the parotid gland, or lacking adequate information. A search of the available literature yielded only 13 documented cases,3-‘oand the clinical features are summarized in Table I. Primary malignant melanoma of the parotid gland arises from melanocytes present in the normal tissue of this organ. This was demonstrated by Greene and Bernier,6 studying normal human parotid gland tissue stained by the dopa method. These authors suggested two criteria for ruling out the possibility of metastatic melanoma in the parotid gland: (1) histopathologic demonstration of malignant melanoma in the parotid gland and (2) inability to demonstrate any other primary origin of the tumor. In the present case these criteria were demonstrated. The diagnosis of malignant melanoma was established by histochemical and immunohistochemical examination, which gave positive results for melanoma cells. Dopa reaction was not performed, becausethe material was fixed in formalin. No further evidence of disease in any other body sites was disclosed after detailed clinical investigation. Greene and Bernie&’ also emphasized that metastatic lesions appear either in parotid lymph nodes or as well-delineated lesions in the parotid gland, whereas the primary tumor is infiltrative and poorly demarcated or completely replacing the pa-
Primary malignant melanoma of parotid gland
Volume 70 Number 5
Table
629
I. Cases in the literature of primary malignant melanoma of the parotid gland Age (yr)/sex
Author (yr)
Clinical presentation
Treatment
Metastases
Follow-up
Migneco ( 1934)4
65/M 62/M 77/M
Jorgensen ( 1954)s
77/M
PM PM PM, firm, fixed PM
Greene and Bernier (1961)6
67/M
PM
P RT Excision
28/M
PM
P
Widespread in body
41/M 66/F 63/F
PM PM, firm PM, firm, fixed PM
P P Enucleation
None None None
R, 7 and 18 mo; DOD, 3.5 yr R, 2 mo; DOD, 4 yr NED, 4 yr NED, 3 yr
Enucleation, RT P, neck dissection, RT (100 Gy), chemotherapy, BCG immunotherapy P, RT (105 Gy) P, RT (48 Gy) P, BCG immunotherapy
CLN
Not reported
CLN, 1 yr; lungs, 3 yr
R, 1 and 1.5 and 3 yr; DOD, 3 yr
None Lung, 8 mo None
NED, 10 mo DOD, 8 mo NED, 4 yr
Delaini (1910)3
Marchegiani
( 1963)7
Cirri and Anderetta (1967)s Brocheriou et al. (1978)9
Konevalov (1978)‘O Our case BCG. Bacille Calmette-G∈ currence; RT, radiotherapy.
72/F 22/M
PM, firm, fixed
47/F 65/M 28/F
PM, firm PM, soft PM, firm, fixed
Excision Excision P
None None Lung
Died, 7 mo from ileus R, 2 mo; DOD, 4 mo; DOD, 6 mo
CLN
Died, 7 wk from MI
Cerebral
DOD, 1 yr
CLN, cervical lymph nodes; DOD, died of disease;NED, no evidence of disease;P. parotidectomy; PM. parotid mass;R, re-
rotid gland. This description parallels the gross and microscopic features in our case. In all the reviewed casesthe main clinical presentation was a progressively enlarging asymptomatic massin the area of the parotid gland, usually firm and fixed by skin and/or deep structures. Only one of the patients displayed initially persistent facial nerve paralysis. Metastases, regional or distant, developed in sevenpatients: three in the regional cervical nodesand four in other body sites, with the lungs being most frequently involved. Surgery, radiation therapy, chemotherapy, and immunotherapy, alone or in combination, were employed in the treatment protocols for the casesin the literature. All 14 patients were treated surgically with procedures varying from wide local excision to total parotidectomy. Four patients had local recurrences. Unless the patient has metastatic melanoma, radical surgery is the initial treatment of choice. However, primary excision is likely to be inadequate becauseof the site of the tumor and the fact that melanoma often extends beyond the visible lesion. It is important to perform frozen sections to verify the adequacy of the surgical margins and to study the entire primary
lesion by subserial section analysis. This may help to preclude sampling error and thereby reduce the rate of recurrence and metastasis. The question whether prophylactic lymph node dissection is of great value is still controversial.14-‘6 Six patients received adjuvant therapy. The benefit of radiotherapy, chemotherapy, and immunotherapy is limited and unclear, becausethe effect on the six patients described indicates no consistent relationship between the type or complexity of therapy and survival rate. The recognition of primary malignant melanoma of the parotid gland has great clinical significance, because a primary lesion is amenable to appropriate surgical treatment, whereas a metastatic lesion cannot be treated successfully and is always fatal. Follow-up information was available on 11 patients; period of survival ranged from 6 months to 4 years, with a mean of 2.3 years. Five patients are alive and free of disease 10 months to 4 years after treatment. Of the four patients known to have died of their disease,period of survival ranged from 8 months to 3% years. The premature death of two patients precludes survival analysis of these cases.In general, the length of follow-up in these 11 caseshas beentoo short
630 Bahar et al. to determine any reliable conclusions as to the effectiveness of various modalities of treatment; however, total excision remains the treatment of choice.
ORAL SURG ORAL MED ORAL PATHOL November 1990
10. 11.
REFERENCES 1. Conley J, Hamaker RC. Melanoma of the head and neck. Laryngoscope 1977;87:460-4. 2. Batakis JG. Tumors of the head and neck. 2nd ed. Baltimore: Williams & Wilkins, 1982:431-47. 3. Delaini F. Di due sarcomi melanotici primitivi della parotide. Rif Med 1910;26:792-6. 4. Migneco A. Sul melanoma della parotide. Arch Ital Chir 1934;36:670-6. 5. Jorgensen MB. Malignant melanoma of the parotid gland. Am J Surg 1954;87:275-7. 6. Greene GW, Bernier JL. Primary malignant melanomas of the parotid gland. Oral Surg 1961;14:108-16. 7. Marchegiani C. In tema di tumori rari delle ghiandole salivari: il melanoma della parotide. Ann Ital Chir 1963;47:1099-111. 8. Cirri GP, Andretta 0. Infrequent tumors of the parotid gland. Arch Ital Path01 Clin 1967;10:397-425. 9. Brocheriou C, Vaillant JM, Szpirglas H, et al. Melanome ma-
12. 13. 14.
15. 16.
lin primitif de la parotide: une observation. Rev Stomatol Chir Maxillofac 1978;79:61-8. Konevalov RV. Melanoma of the parotid salivary gland. Vestn Khir 1978;108:118-9. Conley J, Arena S. Parotid gland as a focus of metastasis. Arch Surg 1963;87:757-64. Nichols RD, Pinnock LA, Szymanowski RT. Metastases to parotid nodes. Laryngoscope 1980;90:1324-8. Remy RA. Tumeur de la parotide. Bull Sot Anat Paris 1875. Ames FC, Sugarbaker EV, Ballantyne AJ. Analysis of surgical and disease control in stage I melanoma of the head and neck. Am J Surg 1976;132:484-91. Olson RM, Woods JE, Soule EH. Regional lymph node management and outcome in 100 patients with head and neck melanoma. Am J Surg 1981;142:470-3. Snow GB, van der Waal I. Mucosal melanomas of the head and neck. Otolaryngol Clin North Am 1986;19:537-47.
Reprint requests to: Dr. M. Bahar Department of Otolaryngology-Head Beilinson Medical Center Petah Tiqva, 49 100, Israel
and Neck Surgery
