- Email: [email protected]
Heterotopic salivary gland tissue in the neck
Heterotopic salivary gland tissue in the neck Anna Haemel, MD,a,b Douglas R. Gnepp, MD,c,e James Carlsten, MD,d and Leslie Robinson-Bostom, MDe,f Madison, Wisconsin; and Providence and Pawtucket, Rhode Island Heterotopic salivary gland tissue (HSGT) consists of salivary tissue outside of the major and minor salivary glands and typically presents as a draining sinus and/or asymptomatic nodule of the neck along the lower anterior sternocleidomastoid muscle. There are a limited number of case series exploring this rare entity. To further delineate the clinicopathologic characteristics of this lesion, we present 11 cases of HSGT in the neck, many with cutaneous involvement. Anatomic pathology files from Lifespan-affiliated hospitals (Rhode Island Hospital and Miriam Hospital) were retrospectively reviewed for all cases meeting criteria for HSGT from 1983 through 2005, and 11 patients were identified: 4 female and 7 male, ages 5 months to 64 years, with 8 patients younger than 18 years; 7 patients presented with a draining sinus. Of note, 8 of 11 cases occurred on the right side. In general, microscopic examination revealed mucinous and serous salivary glandular structures with an associated duct; no cytologic atypia was observed. All cases stained positive for smooth muscle actin and calponin, highlighting a myoepithelial layer similar to that seen in minor and major salivary glands. As in our series, most cases of cervical HSGT occur near the anterior sternocleidomastoid muscle with a right-sided predilection. Cases generally present by early childhood, although 3 cases in our series were diagnosed in adulthood. Although cancers arising in these lesions are fairly uncommon, most clinically apparent foci of HSGT are excised. This entity should be considered in the dermatologist’s differential diagnostic considerations for a draining sinus and a lateral, especially right-sided, neck mass. ( J Am Acad Dermatol 2008;58:251-6.)
T
he neck is developmentally complex, with frequent embryologic anomalies1 most commonly presenting as fistulae along the lower anterior sternocleidomastoid muscle (SCM).2,3 The diagnosis of chronic draining sinuses of the neck can be challenging because of the broad diagnostic considerations,4 including infectious (eg, actinomycosis, Nocardia, and scrofuloderma), inflammatory (eg, dental sinus, acne keloidalis nuchae, and acne conglobata), neoplastic (metastatic or primary carcinomas), and developmental (eg, branchial cleft cysts, thyroglossal duct cysts, and heterotopic salivary gland tissue [HSGT ]) causes.
From the Departments of Medicinea and Dermatology,b University of Wisconsin; Departments of Pathologyc and Dermatology,f the Warren Alpert Medical School of Brown University, Providence; Anatomic Pathology, Memorial Hospital of Rhode Island, Pawtucketd; and Department of Pathology, Rhode Island Hospital, Providence.e Funding sources: None. Conflicts of interest: None declared. Previously partially presented as a poster at the American Academy of Dermatology Summer Academy Meeting, Chicago, Ill, July 21-3, 2005. Reprints not available from the authors. Correspondence to: Leslie Robinson-Bostom, MD, Rhode Island Hospital, APC 10, 593 Eddy St, Providence, RI 02903. E-mail: [email protected]. 0190-9622/$34.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2007.11.009
Abbreviations used: HSGT: heterotopic salivary gland tissue SCM: sternocleidomastoid muscle
HSGT, also known as ectopic or choristomatous salivary gland, consists of salivary tissue found outside of the major and minor salivary glands.5 This rare, frequently congenital lesion typically presents as a draining sinus and/or asymptomatic nodule of the neck along the low anterior SCM.1,3,6 Additional sites have been reported and include the mandible,7 middle ear,8 pituitary,9 parathyroid,10 mediastinum,11 and rectum.12 Fluid production is typically intermittent, may be associated with eating, and appears clear or saliva-like regardless of the substance ingested.1,3,6 The pathogenesis of HSGT of the neck remains uncertain. HSGT in the neck is most widely thought to arise sporadically through defective closure of the precervical sinus of His within the branchial apparatus; this is followed by heteroplasia, or abnormal differentiation of cells into salivary glandular structures, within the ectodermal lining of the sinus.1,6 A probable relationship to the branchial apparatus is supported by the location of lesions along the low anterior SCM, a right-sided predilection shared with other branchial cleft anomalies, occasional bilateral occurrence, and congenital presentation.1,6 Previous authors have considered HSGT appearing alone to 251
Clinical presentation
Case Age Sex
Presenting symptoms
Location
Glandular histopathology
Duration
Type
Ductal histopathology
Maximum lobular No. of dimension, Ductal lobules mm morphology
Ductal epithelial lining
5y
F
Draining sinus
Anterior R SCM
Congenital Predominately mucinous
;3
0.6
Collapsed, Stratified with squamous associated to cuboidal fistulous tract
2
1y
F
Draining sinus
Anterior R SCM
Congenital Predominately serous
Single
2.0
Dilated
3
14 y M
Draining sinus
Anterior L SCM
6-8 y
3.0
Normal
4
64 y M
Draining sinus with associated mass
R suprasternal Congenital Mucinous lower neck, just off midline
;3
1.3
Normal
5
5 mo M
Draining sinus with associated mass
R neck
1 mo
Single
0.65
Dilated
6
2y
Draining sinus
Anterior R SCM
Since 1 wk Predominately Multiple of life mucinous
2.8
Very dilated
M
Serous
Stratified cuboidal to columnar with focal squamous differentiation and apocrine secretion Stratified cuboidal
Periductal inflammation
Degeneration
Mild lymphocytic Present periductal inflammation with necrosis along fistulous tract Moderate Mild lymphocytic and neutrophilic infiltrate
Mild lymphocytic inflammation Moderate lymphocytic inflammation
Present, with pseudostratified columnar epithelium and apocrine change
Mild
Absent
Absent
Absent
Absent
Absent
Absent
Present, with partial degeneration and mild chronic inflammation; lining with spectrum of simple squamous to cuboidal to pseudostratified with cilia
FEBRUARY 2008
Pseudostratified columnar with cilia goblet cells and focal oncocytic change Pseudostratified Very mild mixed columnar with cilia lymphocytic and goblet cells and transitioning neutrophilic to squamous inflammation near epidermis Focal moderate Stratified lymphocytic cuboidal inflammation to columnar with with cilia eosinophils, plasma cells, and one germinal center
Cystic change
Absent
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252 Haemel et al
Table I. Summary of clinicopathologic data for 11 patients with heterotopic salivary gland tissue in the neck
M
Draining sinus
Anterior L SCM
8
5y
M
Painless swelling
Unknown Fluctuant mass R upper neck with small punctum
9
40 y F
Enlarging nodule
Anterior R SCM
10
3y
Dimple
11
58 y F
History of parathyroid adenoma, thyroid nodules, and follicular neoplasm
M
Chronic, Seromucinous duration not specified
5
Dense lymphocytic with germinal centers Moderate lymphocytic inflammation
Absent
Absent
0.9
Slightly dilated
Pseudostratified columnar with cilia and goblet cells
Predominately Multiple serous
3.0
Collapsed
Unknown
Predominately mucinous with focal atrophy
3
3.6
Dilated
L medial clavicle
Unknown
Seromucinous
5
0.4
Collapsed
Adjacent to R inferior parathyroid
Unknown
Serous with interspersed fat; associated with adjacent small mucinous cyst
1
1.3
No duct present
Mild Absent Stratified columnar to stratified squamous with naked vellus hair shafts communicating with epidermis Stratified Mild lymphocytic Present Present, lined with columnar with inflammation with pseudostratified apocrine change cyst wall columnar and focal epithelium cilia with cilia and focal squamous metaplasia with focal apocrine change Pseudostratified Absent Absent Absent columnar with goblet cells No duct No duct No duct No duct present present present present
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F, Female; M, male; L, left; R, right; SCM, sternocleidomastoid muscle.
Haemel et al 253
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Fig 1. Case 3. Heterotopic salivary gland tissue embedded within subcutaneous tissue. Left upper inset, Highlight of myoepithelial layer similar to that seen in minor and major salivary glands. Right upper inset, High-power view demonstrating no cytologic atypia. (Hematoxylin-eosin stain; original magnifications: 340; right upper inset, 3200.) (Left upper inset, Smooth muscle actin stain; original magnification: 3200.)
be an entity distinct from salivary tissue within a branchial cleft cyst.1 However, Chang et al5 recently suggested the embryogenesis of the two lesions is sufficiently intertwined that association with branchial cleft cyst should not be considered exclusion criteria for HSGT. Hsu et al13 reported a family with 5 generations showing cervical HSGT suggesting autosomal dominant inheritance; however, this is the only report of familial occurrence, and lesions typically appear to be sporadic.6 To date, there are a limited number of case series of HSGT in the neck, the largest being a series of 11 cases by Youngs and Scofield6 in 1967 and a more recent series of 5 cases by Lassaletta-Atienza et al1 in 1998. To further delineate the presentation and clinicopathologic characteristics of this rare lesion, we present a series of 11 cases of HSGT in the neck, the majority of which have cutaneous involvement.
Fig 2. Case 5. Pseudostratified columnar epithelium lining duct with adjacent focus of serous type heterotopic salivary glands within fat of subcutaneous tissue. (Hematoxylin-eosin stain; original magnification: 3100.)
Fig 3. Case 2. Reticular dermal salivary gland duct demonstrating epithelial lining ranging from simple cuboidal to stratified squamous and pseudostratified ciliated epithelium. (Hematoxylin-eosin stain; original magnification: 3200.)
actin and calponin to highlight the presence of a myoepithelial layer similar to that seen in minor and major salivary glands. The clinical histories were then reviewed and correlated with the histologic findings.
RESULTS METHODS After approval of the institutional review board at Lifespan-affiliated hospitals (Rhode Island Hospital and Miriam Hospital), a large tertiary care center, anatomic pathology files were searched for all cases containing ‘‘ectopic salivary’’ in the final diagnosis, from 1983 through 2005. Fourteen cases were identified for possible inclusion in this retrospective case series; after an initial review, 3 cases were excluded: one branchial cleft cyst containing salivary rests, one accessory gland, and one case of ectopic bone formation related to an impacted sialolith. Hematoxylin-eosinestained sections of the remaining 11 cases were independently evaluated by two pathologists for glandular and ductal histopathology. The lesions were also stained for smooth muscle
The clinical and pathologic findings for the 11 cases are summarized in Table I. There were 4 female and 7 male patients, with age range at surgery from 5 months to 64 years (median 5 years). In 5 of the cases, the lesion was noted within the first month of life. Patients presented with sinuses that had intermittent drainage, localized nodules, or a dimple. In one case ectopic salivary tissue was an incidental finding related to a parathyroidectomy. Eight cases occurred on the right side of the neck. Of note, case 3 was associated with a branchial cleft remnant on the opposite side, which also contained seromucinous glands. In general, microscopic examination revealed typical mucinous and serous salivary glandular structures with an associated duct (Figs 1 to 3). The duct was dilated in 5 cases, and the ductal
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epithelium ranged from simple squamous to pseudostratified columnar epithelium with cilia and goblet cells; one case demonstrated focal apocrine change. Periductal chronic inflammation was present in 9 cases with several cases also demonstrating acute inflammatory changes. Three cases showed mild degeneration of the associated duct and 3 had associated cystic change. All cases stained positive for smooth muscle actin and calponin. There was no evidence of malignancy in any of the cases examined; all were treated with simple excision.
DISCUSSION HSGT of the neck should remain within the dermatologist’s differential diagnosis for draining sinus for all age groups. Although most lesions in this series were noted at birth or early in childhood, identification may not occur until later in life because of the small size of the draining orifices3 and the relative rarity of pain and infection compared with that associated with branchial cleft fistulas13,14; one patient delayed treatment until 64 years of age in spite of the congenital nature of his lesion. The occurrence near the anterior SCM and rightsided predilection observed in this series are typical.3 Although there are multiple cases in which cervical HSGT has occurred bilaterally,3,6 all lesions in this series were unilateral. One patient did have a contralateral branchial cleft cyst also containing salivary rests. A similar case in which simple HSGT was associated with a contralateral branchial cleft sinus containing salivary tissue has been reported by Goodman et al.15 The association of these anomalies supports the interrelated embryogenesis of these two lesions.5,15 However, association with other additional congenital anomalies is rare.3 The relationship between HSGT and salivary rests occurring within branchial cleft anomalies, which are known to differentiate into various tissues, remains controversial. Lesions meeting criteria for the latter5 were excluded from this series based on earlier suggestions that the two entities should be considered distinct.1 Of note, on the basis of these criteria, Lassaletta-Atienza et al1 suggest that lesions in some earlier series, including one case in the series of Youngs and Scofield,6 should not be considered true HSGT. Regardless of whether an understanding of common embryogenesis may now warrant unification into a single diagnostic category,5 we believe determining whether salivary tissue occurs in association with a branchial cleft cyst will remain clinically relevant. HSGT is typically treated with excision for diagnostic and cosmetic purposes and to prevent complications, such as neoplastic transformation. Compared with surgery for branchial cleft cysts,
treatment of pure HSGT is more straightforward; the sinus tracts are generally shorter and may not extend upward toward the major vasculature of the neck.1,13 A sinugram can help to define the lesion preoperatively and typically shows a short tract ending in a blush suggestive of a gland14,16,17; however, the study may be unsuccessful because of fibrosis.5 Although biopsy of the sinus opening may help to distinguish HSGT from infectious or neoplastic causes, it may not differentiate the lesion from other developmental causes, and the diagnosis may rely on microscopic examination of the entire surgical specimen. Mixed glands predominated in this series, in agreement with past observations that mixed and mucinous glands are most common.1,3,14,18 However, pure serous glands (similar to those of the parotid) were also identified in 3 of our cases, lending further support to the diversity afforded by a heteroplastic embryologic mechanism.14 The presence of a myoepithelial layer similar to that seen in minor and major salivary glands was also highlighted in all cases by positive staining with smooth muscle actin and calponin. Some of the variation seen within the associated ducts, such as areas of squamous metaplasia, may be related to chronic inflammation secondary to physical pressure of retained mucus.15 Mucus retention within HSGT has been compared with that within mucoceles; this may account for the ductal dilation and cyst formation we observed in several cases.5 The periductal lymphocyte infiltrate observed in many of our cases is well described in the literature.3,6 However, an association with prominent lymphoid tissue beneath the epithelium has been considered criteria for branchial cleft cyst.5 Although two cases in this series demonstrated germinal centers, extensive or encapsulated lymphoid tissue was not found. While there was no evidence of neoplastic change in any of the 11 cases examined, the full spectrum of salivary gland tumors may occur in HSGT, and specimens should be examined for neoplastic transformation. Tumors are rare and benign 80% of the time.19,20 However, a malignant primary tumor in a heterotopic site should be considered when salivary carcinoma is identified outside the areas of the major and minor salivary glands. These heterotopic tumors must be differentiated from metastatic disease through a careful search and treated accordingly.19,20 HSGT is a rare diagnosis, although whether this is a result of a truly low incidence or the result of infrequent clinical presentation is unclear.21 Because of the rarity of this lesion, retrospective chart review at a large tertiary care center is a practical, costeffective means for further characterization of this lesion. Nonetheless, limitations of this approach
256 Haemel et al
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include incomplete recording of all relevant clinical data, such as clinical photographs and several pieces of the clinical history. In summary, this is one of the largest series to date describing HSGT in the neck. Despite its rarity, inclusion of this unusual entity in the differential diagnosis of draining sinuses of the neck may minimize potential complications and help in the further characterization of this lesion. REFERENCES 1. Lassaletta-Atienza L, Lopez-Rios F, Martin G, Benito A, Bronchalo F, Martinez-Tello FJ, et al. Salivary gland heterotopia in the lower neck: a report of five cases. Int J Pediatr Otorhinolaryngol 1998;43:153-61. 2. Doi O, Hutson JM, Myers NA, McKelvie PA. Branchial remnants: a review of 58 cases. J Pediatr Surg 1988;23:789-92. 3. Mair IW, Bjorang G, Kearney MS. Heterotopic cervical salivary glands. J Laryngol Otol 1977;91:35-40. 4. Cioffi GA, Terezhalmy GT, Parlette HL. Cutaneous draining sinus tract: an odontogenic etiology. J Am Acad Dermatol 1986;14:94-100. 5. Chang WY, Lee KW, Tsai KB, Chen GS. Heterotopic salivary gland tissue: a case report demonstrating evolution and association with the branchial apparatus. J Dermatol 2005;32:731-6. 6. Youngs LA, Scofield HH. Heterotopic salivary gland tissue in the lower neck. Arch Pathol 1967;83:550-6. 7. Afanas’ev VV, Starodubtsev VS. Salivary gland heterotopia in the bone tissue of the mandible [Russian]. Stomatologiia (Mosk) 1995; 74:69-70. 8. Enoz M, Suoglu Y. Salivary gland choristoma of the middle ear. Laryngoscope 2006;116:1033-4.
9. Tatter SB, Edgar MA, Klibanski A, Swearingen B. Symptomatic salivary-rest cyst of the sella turcica. Acta Neurochir (Wien) 1995;135:150-3. 10. Edwards PC, Bhuiya T, Kahn LB, Fantasia JE. Salivary heterotopia of the parathyroid gland: a report of two cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:590-3. 11. Feigin GA, Robinson B, Marchevsky A. Mixed tumor of the mediastinum. Arch Pathol Lab Med 1986;110:80-1. 12. Weitzner S. Ectopic salivary gland tissue in submucosa of rectum. Dis Colon Rectum 1983;26:814-7. 13. Hsu RF, Hsu YC, Huang SC. Hereditary ectopic salivary gland: survey of three generations. Acta Otolaryngol 2006;126: 330-3. 14. Stingle WH, Priebe CJ Jr. Ectopic salivary gland and sinus in the lower neck. Ann Otol Rhinol Laryngol 1974;83:379-81. 15. Goodman RS, Daly JF, Valensi Q. Heterotopic salivary tissue and branchial cleft sinus. Laryngoscope 1981;91:260-4. 16. Soucy P. Congenital cervical salivary fistula. Can J Surg 1985;28:130-1. 17. Marshall JN, Soo G, Coakley FV. Ectopic salivary gland in the posterior triangle of the neck. J Laryngol Otol 1995;109:669-70. 18. Mair IW, Bjorang G, Kearney MS. Lateral cervical anomalies and salivary heterotopia. Clin Otolaryngol 1979;4:175-82. 19. Ferlito A, Bertino G, Rinaldo A, Mannara GM, Devaney KO. A review of heterotopia and associated salivary gland neoplasms of the head and neck. J Laryngol Otol 1999; 113:299-303. 20. Daniel E, McGuirt WF Sr. Neck masses secondary to heterotopic salivary gland tissue: a 25-year experience. Am J Otolaryngol 2005;26:96-100. 21. Romano JF, Marino CT. Heterotopic salivary tissue at the base of the neck. Int J Dermatol 1982;21:42-3.
T
he neck is developmentally complex, with frequent embryologic anomalies1 most commonly presenting as fistulae along the lower anterior sternocleidomastoid muscle (SCM).2,3 The diagnosis of chronic draining sinuses of the neck can be challenging because of the broad diagnostic considerations,4 including infectious (eg, actinomycosis, Nocardia, and scrofuloderma), inflammatory (eg, dental sinus, acne keloidalis nuchae, and acne conglobata), neoplastic (metastatic or primary carcinomas), and developmental (eg, branchial cleft cysts, thyroglossal duct cysts, and heterotopic salivary gland tissue [HSGT ]) causes.
From the Departments of Medicinea and Dermatology,b University of Wisconsin; Departments of Pathologyc and Dermatology,f the Warren Alpert Medical School of Brown University, Providence; Anatomic Pathology, Memorial Hospital of Rhode Island, Pawtucketd; and Department of Pathology, Rhode Island Hospital, Providence.e Funding sources: None. Conflicts of interest: None declared. Previously partially presented as a poster at the American Academy of Dermatology Summer Academy Meeting, Chicago, Ill, July 21-3, 2005. Reprints not available from the authors. Correspondence to: Leslie Robinson-Bostom, MD, Rhode Island Hospital, APC 10, 593 Eddy St, Providence, RI 02903. E-mail: [email protected]. 0190-9622/$34.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2007.11.009
Abbreviations used: HSGT: heterotopic salivary gland tissue SCM: sternocleidomastoid muscle
HSGT, also known as ectopic or choristomatous salivary gland, consists of salivary tissue found outside of the major and minor salivary glands.5 This rare, frequently congenital lesion typically presents as a draining sinus and/or asymptomatic nodule of the neck along the low anterior SCM.1,3,6 Additional sites have been reported and include the mandible,7 middle ear,8 pituitary,9 parathyroid,10 mediastinum,11 and rectum.12 Fluid production is typically intermittent, may be associated with eating, and appears clear or saliva-like regardless of the substance ingested.1,3,6 The pathogenesis of HSGT of the neck remains uncertain. HSGT in the neck is most widely thought to arise sporadically through defective closure of the precervical sinus of His within the branchial apparatus; this is followed by heteroplasia, or abnormal differentiation of cells into salivary glandular structures, within the ectodermal lining of the sinus.1,6 A probable relationship to the branchial apparatus is supported by the location of lesions along the low anterior SCM, a right-sided predilection shared with other branchial cleft anomalies, occasional bilateral occurrence, and congenital presentation.1,6 Previous authors have considered HSGT appearing alone to 251
Clinical presentation
Case Age Sex
Presenting symptoms
Location
Glandular histopathology
Duration
Type
Ductal histopathology
Maximum lobular No. of dimension, Ductal lobules mm morphology
Ductal epithelial lining
5y
F
Draining sinus
Anterior R SCM
Congenital Predominately mucinous
;3
0.6
Collapsed, Stratified with squamous associated to cuboidal fistulous tract
2
1y
F
Draining sinus
Anterior R SCM
Congenital Predominately serous
Single
2.0
Dilated
3
14 y M
Draining sinus
Anterior L SCM
6-8 y
3.0
Normal
4
64 y M
Draining sinus with associated mass
R suprasternal Congenital Mucinous lower neck, just off midline
;3
1.3
Normal
5
5 mo M
Draining sinus with associated mass
R neck
1 mo
Single
0.65
Dilated
6
2y
Draining sinus
Anterior R SCM
Since 1 wk Predominately Multiple of life mucinous
2.8
Very dilated
M
Serous
Stratified cuboidal to columnar with focal squamous differentiation and apocrine secretion Stratified cuboidal
Periductal inflammation
Degeneration
Mild lymphocytic Present periductal inflammation with necrosis along fistulous tract Moderate Mild lymphocytic and neutrophilic infiltrate
Mild lymphocytic inflammation Moderate lymphocytic inflammation
Present, with pseudostratified columnar epithelium and apocrine change
Mild
Absent
Absent
Absent
Absent
Absent
Absent
Present, with partial degeneration and mild chronic inflammation; lining with spectrum of simple squamous to cuboidal to pseudostratified with cilia
FEBRUARY 2008
Pseudostratified columnar with cilia goblet cells and focal oncocytic change Pseudostratified Very mild mixed columnar with cilia lymphocytic and goblet cells and transitioning neutrophilic to squamous inflammation near epidermis Focal moderate Stratified lymphocytic cuboidal inflammation to columnar with with cilia eosinophils, plasma cells, and one germinal center
Cystic change
Absent
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Seromucinous Multiple
252 Haemel et al
Table I. Summary of clinicopathologic data for 11 patients with heterotopic salivary gland tissue in the neck
M
Draining sinus
Anterior L SCM
8
5y
M
Painless swelling
Unknown Fluctuant mass R upper neck with small punctum
9
40 y F
Enlarging nodule
Anterior R SCM
10
3y
Dimple
11
58 y F
History of parathyroid adenoma, thyroid nodules, and follicular neoplasm
M
Chronic, Seromucinous duration not specified
5
Dense lymphocytic with germinal centers Moderate lymphocytic inflammation
Absent
Absent
0.9
Slightly dilated
Pseudostratified columnar with cilia and goblet cells
Predominately Multiple serous
3.0
Collapsed
Unknown
Predominately mucinous with focal atrophy
3
3.6
Dilated
L medial clavicle
Unknown
Seromucinous
5
0.4
Collapsed
Adjacent to R inferior parathyroid
Unknown
Serous with interspersed fat; associated with adjacent small mucinous cyst
1
1.3
No duct present
Mild Absent Stratified columnar to stratified squamous with naked vellus hair shafts communicating with epidermis Stratified Mild lymphocytic Present Present, lined with columnar with inflammation with pseudostratified apocrine change cyst wall columnar and focal epithelium cilia with cilia and focal squamous metaplasia with focal apocrine change Pseudostratified Absent Absent Absent columnar with goblet cells No duct No duct No duct No duct present present present present
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F, Female; M, male; L, left; R, right; SCM, sternocleidomastoid muscle.
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Fig 1. Case 3. Heterotopic salivary gland tissue embedded within subcutaneous tissue. Left upper inset, Highlight of myoepithelial layer similar to that seen in minor and major salivary glands. Right upper inset, High-power view demonstrating no cytologic atypia. (Hematoxylin-eosin stain; original magnifications: 340; right upper inset, 3200.) (Left upper inset, Smooth muscle actin stain; original magnification: 3200.)
be an entity distinct from salivary tissue within a branchial cleft cyst.1 However, Chang et al5 recently suggested the embryogenesis of the two lesions is sufficiently intertwined that association with branchial cleft cyst should not be considered exclusion criteria for HSGT. Hsu et al13 reported a family with 5 generations showing cervical HSGT suggesting autosomal dominant inheritance; however, this is the only report of familial occurrence, and lesions typically appear to be sporadic.6 To date, there are a limited number of case series of HSGT in the neck, the largest being a series of 11 cases by Youngs and Scofield6 in 1967 and a more recent series of 5 cases by Lassaletta-Atienza et al1 in 1998. To further delineate the presentation and clinicopathologic characteristics of this rare lesion, we present a series of 11 cases of HSGT in the neck, the majority of which have cutaneous involvement.
Fig 2. Case 5. Pseudostratified columnar epithelium lining duct with adjacent focus of serous type heterotopic salivary glands within fat of subcutaneous tissue. (Hematoxylin-eosin stain; original magnification: 3100.)
Fig 3. Case 2. Reticular dermal salivary gland duct demonstrating epithelial lining ranging from simple cuboidal to stratified squamous and pseudostratified ciliated epithelium. (Hematoxylin-eosin stain; original magnification: 3200.)
actin and calponin to highlight the presence of a myoepithelial layer similar to that seen in minor and major salivary glands. The clinical histories were then reviewed and correlated with the histologic findings.
RESULTS METHODS After approval of the institutional review board at Lifespan-affiliated hospitals (Rhode Island Hospital and Miriam Hospital), a large tertiary care center, anatomic pathology files were searched for all cases containing ‘‘ectopic salivary’’ in the final diagnosis, from 1983 through 2005. Fourteen cases were identified for possible inclusion in this retrospective case series; after an initial review, 3 cases were excluded: one branchial cleft cyst containing salivary rests, one accessory gland, and one case of ectopic bone formation related to an impacted sialolith. Hematoxylin-eosinestained sections of the remaining 11 cases were independently evaluated by two pathologists for glandular and ductal histopathology. The lesions were also stained for smooth muscle
The clinical and pathologic findings for the 11 cases are summarized in Table I. There were 4 female and 7 male patients, with age range at surgery from 5 months to 64 years (median 5 years). In 5 of the cases, the lesion was noted within the first month of life. Patients presented with sinuses that had intermittent drainage, localized nodules, or a dimple. In one case ectopic salivary tissue was an incidental finding related to a parathyroidectomy. Eight cases occurred on the right side of the neck. Of note, case 3 was associated with a branchial cleft remnant on the opposite side, which also contained seromucinous glands. In general, microscopic examination revealed typical mucinous and serous salivary glandular structures with an associated duct (Figs 1 to 3). The duct was dilated in 5 cases, and the ductal
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epithelium ranged from simple squamous to pseudostratified columnar epithelium with cilia and goblet cells; one case demonstrated focal apocrine change. Periductal chronic inflammation was present in 9 cases with several cases also demonstrating acute inflammatory changes. Three cases showed mild degeneration of the associated duct and 3 had associated cystic change. All cases stained positive for smooth muscle actin and calponin. There was no evidence of malignancy in any of the cases examined; all were treated with simple excision.
DISCUSSION HSGT of the neck should remain within the dermatologist’s differential diagnosis for draining sinus for all age groups. Although most lesions in this series were noted at birth or early in childhood, identification may not occur until later in life because of the small size of the draining orifices3 and the relative rarity of pain and infection compared with that associated with branchial cleft fistulas13,14; one patient delayed treatment until 64 years of age in spite of the congenital nature of his lesion. The occurrence near the anterior SCM and rightsided predilection observed in this series are typical.3 Although there are multiple cases in which cervical HSGT has occurred bilaterally,3,6 all lesions in this series were unilateral. One patient did have a contralateral branchial cleft cyst also containing salivary rests. A similar case in which simple HSGT was associated with a contralateral branchial cleft sinus containing salivary tissue has been reported by Goodman et al.15 The association of these anomalies supports the interrelated embryogenesis of these two lesions.5,15 However, association with other additional congenital anomalies is rare.3 The relationship between HSGT and salivary rests occurring within branchial cleft anomalies, which are known to differentiate into various tissues, remains controversial. Lesions meeting criteria for the latter5 were excluded from this series based on earlier suggestions that the two entities should be considered distinct.1 Of note, on the basis of these criteria, Lassaletta-Atienza et al1 suggest that lesions in some earlier series, including one case in the series of Youngs and Scofield,6 should not be considered true HSGT. Regardless of whether an understanding of common embryogenesis may now warrant unification into a single diagnostic category,5 we believe determining whether salivary tissue occurs in association with a branchial cleft cyst will remain clinically relevant. HSGT is typically treated with excision for diagnostic and cosmetic purposes and to prevent complications, such as neoplastic transformation. Compared with surgery for branchial cleft cysts,
treatment of pure HSGT is more straightforward; the sinus tracts are generally shorter and may not extend upward toward the major vasculature of the neck.1,13 A sinugram can help to define the lesion preoperatively and typically shows a short tract ending in a blush suggestive of a gland14,16,17; however, the study may be unsuccessful because of fibrosis.5 Although biopsy of the sinus opening may help to distinguish HSGT from infectious or neoplastic causes, it may not differentiate the lesion from other developmental causes, and the diagnosis may rely on microscopic examination of the entire surgical specimen. Mixed glands predominated in this series, in agreement with past observations that mixed and mucinous glands are most common.1,3,14,18 However, pure serous glands (similar to those of the parotid) were also identified in 3 of our cases, lending further support to the diversity afforded by a heteroplastic embryologic mechanism.14 The presence of a myoepithelial layer similar to that seen in minor and major salivary glands was also highlighted in all cases by positive staining with smooth muscle actin and calponin. Some of the variation seen within the associated ducts, such as areas of squamous metaplasia, may be related to chronic inflammation secondary to physical pressure of retained mucus.15 Mucus retention within HSGT has been compared with that within mucoceles; this may account for the ductal dilation and cyst formation we observed in several cases.5 The periductal lymphocyte infiltrate observed in many of our cases is well described in the literature.3,6 However, an association with prominent lymphoid tissue beneath the epithelium has been considered criteria for branchial cleft cyst.5 Although two cases in this series demonstrated germinal centers, extensive or encapsulated lymphoid tissue was not found. While there was no evidence of neoplastic change in any of the 11 cases examined, the full spectrum of salivary gland tumors may occur in HSGT, and specimens should be examined for neoplastic transformation. Tumors are rare and benign 80% of the time.19,20 However, a malignant primary tumor in a heterotopic site should be considered when salivary carcinoma is identified outside the areas of the major and minor salivary glands. These heterotopic tumors must be differentiated from metastatic disease through a careful search and treated accordingly.19,20 HSGT is a rare diagnosis, although whether this is a result of a truly low incidence or the result of infrequent clinical presentation is unclear.21 Because of the rarity of this lesion, retrospective chart review at a large tertiary care center is a practical, costeffective means for further characterization of this lesion. Nonetheless, limitations of this approach
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include incomplete recording of all relevant clinical data, such as clinical photographs and several pieces of the clinical history. In summary, this is one of the largest series to date describing HSGT in the neck. Despite its rarity, inclusion of this unusual entity in the differential diagnosis of draining sinuses of the neck may minimize potential complications and help in the further characterization of this lesion. REFERENCES 1. Lassaletta-Atienza L, Lopez-Rios F, Martin G, Benito A, Bronchalo F, Martinez-Tello FJ, et al. Salivary gland heterotopia in the lower neck: a report of five cases. Int J Pediatr Otorhinolaryngol 1998;43:153-61. 2. Doi O, Hutson JM, Myers NA, McKelvie PA. Branchial remnants: a review of 58 cases. J Pediatr Surg 1988;23:789-92. 3. Mair IW, Bjorang G, Kearney MS. Heterotopic cervical salivary glands. J Laryngol Otol 1977;91:35-40. 4. Cioffi GA, Terezhalmy GT, Parlette HL. Cutaneous draining sinus tract: an odontogenic etiology. J Am Acad Dermatol 1986;14:94-100. 5. Chang WY, Lee KW, Tsai KB, Chen GS. Heterotopic salivary gland tissue: a case report demonstrating evolution and association with the branchial apparatus. J Dermatol 2005;32:731-6. 6. Youngs LA, Scofield HH. Heterotopic salivary gland tissue in the lower neck. Arch Pathol 1967;83:550-6. 7. Afanas’ev VV, Starodubtsev VS. Salivary gland heterotopia in the bone tissue of the mandible [Russian]. Stomatologiia (Mosk) 1995; 74:69-70. 8. Enoz M, Suoglu Y. Salivary gland choristoma of the middle ear. Laryngoscope 2006;116:1033-4.
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