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Epithelial-myoepithelial carcinoma arising in the submandibular gland: A case report with immunohistochemical study
j Oral Maxillofac Surg 58:98-102, 2000
Epithelial-Myoepithelial Carcinoma Arising in the Submandibular Gland: A Case Report With I m m u n o h i s t o c h e m i c a l Study Hiroyuki Kaneko, DDS, PhD, * Takashi Muramatsu, DDS, ehO, t Hideki Ogiuchi, DDS, PhD,¢ and Masaki Shimono, DDS, PhD~ E p i t h e l i a l - m y o e p i t h e l i a l c a r c i n o m a (EMC) is a r a r e m a l i g n a n t t u m o r , w h i c h c o n s t i t u t e s a p p r o x i m a t e l y 1% o f all salivary g l a n d t u m o r s . 1 T h i s t u m o r w a s establ i s h e d as a d i s t i n c t c l i n i c o p a t h o l o g i c e n t i t y b y t h e W o r l d H e a l t h O r g a n i z a t i o n in 1991. 2 M o s t c a s e s o f EMC o c c u r p r e d o m i n a n t l y in t h e p a r o t i d g l a n d a n d s h o w a p r e d i l e c t i o n f o r f e m a l e s , w i t h a p e a k incid e n c e in t h e s e v e n t h o r e i g h t h d e c a d e o f life. 14 I n this r e p o r t , a r a r e c a s e o f EMC arising in t h e left s u b m a n d i b u l a r g l a n d in a r e l a t i v e l y y o u n g p a t i e n t is pres e n t e d . In a d d i t i o n , t h e t u m o r w a s s t u d i e d h i s t o c h e m i cally a n d i m m u n o h i s t o c h e m i c a U y .
Report of Case A 29-year-old, otherwise healthy, Japanese w o m a n was admitted to Tokyo W o m e n ' s Medical University hospital for surgical removal of a tumor on February 4, 1994. She had b e c o m e aware of slight swelling in the left submandibular region about 2 years previously and had visited a neighboring dental clinic w h e r e the submandibular swelling was attributed to pericoronitis of the left lower third molar. In January 1994, the left submandibular swelling began to gradually increase in size; therefore, she visited the hospital. The mass, measuring 2 × 1 cm, was located in the left submandibular region and was elastic hard (Fig 1). Intraoral examination indicated no swelling, redness, or disturbance
FIGURE ! • A clinical view of the tumor located in the left submandibular region.
*Assistant Professor, Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, School of Medicine, Japan. tAssistant Professor, Department of Pathology, Tokyo Dental College, Japan. ¢Professor, Department of Oral and MaxiUofacial Surgery, Tokyo Women's Medical University, School of Medicine, Japan. ]Professor, Department of Pathology, Tokyo Dental College, Japan. Address correspondence and reprint requests to Dr Kaneko: Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, School of Medicine, 8-1 Kawada-cho, ShinjukuKu, Tokyo, 162-8666 Japan; e-mail: [email protected] © 2000 American Associationof Oral and Maxillofacid Surgeons 0278-2391/00/5801-001653 0 0 / 0
FIGURE 2. A C T scan shows a high-densit~ mass in the posterior region of the left submandibular g)and (arrow). This contained highdensity areas resembling calcification (arrowhead).
98
99
KANEKO ET AL
2
3
4
5
6
7
FIGURE 3. The cut surface of the tumor shows a solid, pale-yellow mass with partially formed cyst-like spaces.
of salivary secretion. C o m p u t e d tomography s h o w e d a mass of higher density than the submandibular gland located in the posterior part of the gland. The mass had a comparatively well-defined border and the contents w e r e heterogeneous, including high-density areas of apparent calcification (Fig 2). Based on a clinical diagnosis of a benign salivary gland tumor, resection of the lesion was performed under general anesthesia on March 10, 1994. The resected s p e c i m e n measured 2.5 x 1.5 x 1.3 cm and was irregularly shaped and paie-red. The cut surface was solid and paie-yellow, with partially formed cyst-like spaces (Fig 3). She was discharged from the hospital on March 16, without any clinical symptoms.
PATHOLOGIC FINDINGS The resected tissue was fixed in 10% neutral btfffered formalin, e m b e d d e d in paraffin, and processed for routine
histologic examination. The tumor was surrounded in part by a thin fibrous capsule and c o m p o s e d of double-layered, tubule-like structures formed by inner eosinophilic ductal cells and outer clear cells, as well by solid clear cells, and spindle-shaped cells (Fig 4). Occasionally, the tumor formed solid sheets and small cysts. Solid clear cells w e r e rarer than biphasic clear cells. These clear cells had oval or polygonal cytoplasm and s h o w e d cellular polymorphism, but nuclear atypia was rarely seen. In parts of the tumor, a fibrous capsule was not present, and the clear cells invaded the adjacent submandibular gland (Fig 5). Myxoid or hyalinized stroma was occasionally observed among the tumor cells, as well as infiltration of a few inflammatory cells (Fig 6). Various-sized calcifications w e r e scattered in the stroma. For histochemical study, periodic-acid-Shift (PAS) and mucicarmine stainings w e r e used. Polyclonal keratin (PK), epithelial m e m b r a n e antigen (EMA), S-IOO protein, smooth muscle actin (HHF35), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), amylase, lactoferrin (LF), secretory c o m p o n e n t (SC), and vimentin w e r e used as primary antibodies for immunohistochemical study. These primary antibodies w e r e processed by the streptavidinbiotin (SAB) method. The inner eosinophilic cells of the tubule-like structures w e r e positive for PK, EMA, SC, and amylase (Fig 7). Clear cells that showed both solid and tubular growth reacted with S-IO0, GFAP, and vimentin (Fig 8), and had diastase-soluble PAS granules in their cytoplasm. A few solid clear cells s h o w e d positivity for HHF35. No cells positive for NSE, LF, or mucicarmine staining w e r e observed. The tumor was diagnosed as EMC arising in the submandibular gland.
Discussion EMC w a s first d e s c r i b e d b y D o n a t h et al in 1972. 7 It is g e n e r a l l y a c c e p t e d t h a t EMC w a s p r e v i o u s l y reported under a variety of names, including adenomyoepithelioma, glycogen-rich adenoma, glycogen-rich
FIGURE 4. The tumor component is composed of biphasic structures formed by inner epithelial cells and outer clear cells (HE stain, original magnification x 100).
] O0
EMC ARISING IN THE SUBMANDIBULAR GLAND
FIGURE 5. Clear tumor cells invade the adjacent submandibulargland, and the remainingacini can be observed (arrowheads) (HE stain, original magnification x 100).
c a r c i n o m a , c l e a r cell a d e n o m a , a n d c l e a r cell carcin o m a . 1,6,s,9 H o w e v e r , EMC w a s listed in t h e r e c e n t W o r l d Health O r g a n i z a t i o n classification as a distinct c l i n i c o p a t h o l o g i c entity. 2 F r o m 70% to 80% o f EMCs o c c u r in t h e p a r o t i d gland, w i t h a p r e d i l e c t i o n for females. M o r e o v e r , EMC o c c u r s p r e d o m i n a n t l y in t h e s e v e n t h o r e i g h t h d e c a d e o f life, a n d t h e m e a n age o f p a t i e n t s is a p p r o x i m a t e l y 60 years. 1-3,10 To o u r k n o w l e d g e , m o r e t h a n 140 cases o f EMC have b e e n r e p o r t e d in t h e English literature. 3,s,9,11-19 Of
t h e s e cases, 12 o c c u r r e d in t h e s u b m a n d i b u l a r gland~,5,7,9,1°,2°,21; this c o n s t i t u t e s 8.6% o f all EMC cases. T h e o c c u r r e n c e is similar to that p r e v i o u s l y r e p o r t e d . 1 T h e cases r e p o r t s o f EMC arising in t h e s u b m a n d i b u l a r g l a n d that h a d sufficient i n f o r m a t i o n are s h o w n in Table 1. A m o n g EMC cases in t h e p a r o t i d gland, 6 p a t i e n t s w e r e u n d e r 30 y e a r o f age, a n d t h e y o u n g e s t p a t i e n t w a s an 8-year-old boy. H o w e v e r , in t h e s u b m a n d i b u l a r g l a n d cases, t h e ages r a n g e d f r o m 65 to 103 years, w i t h a m e a n age o f 71 years. T h e
FIGURE 6. Myxoid and hyalinized stroma are occasionallyobserved (HE stain, original magnification x 100).
KANEKO ET AL
]0 1
FIGURE 7. The inner ductal cells are positive for polyclonal keratin (original magnification x 4 0 0 )
gender distribution was 4 males and 3 females. Therefore, the current case may be the youngest reported patient with EMC arising in the submandibular gland. Local recurrence occurred in 4 cases of EMC in the submandibular gland, but distant metastases appeared in only 1 case involving a supraclavicular lymph node. EMC is generally considered to be a low-grade malignant neoplasm that recurs frequently at local sites, but distant metastasis is extremely rare. Previous studies have shown that 40% of EMC cases have recurred at
local sites and 17% have metastasized to regional lymph nodes.l,3,5 Accordingly, the prognosis for EMC shows no differences between those arising in the submandibular gland and in other sites. Based on the immunohistochemical observations, the inner eosinophilic cells of biphasic proliferation reacted with epithelial and secretory markers, and the outer clear cells were positive for myoepithelial markers. This reactivity is similar to that previously reported. 1,4,8,9 The findings suggest that this tumor
FIGURE 8. The outer clear cells react with S 100 (original magnification x 4 0 0 )
] 02
EMC ARISING IN THE S U B M A N D I B ~
Authors
Age
Sex
Size ( m m )
Aora et al Simpson et al Cho et al
65 103 77 67 72 74 29
M F F M F M F
40 × 20 60 × 50 × 30
Tralongo et al Present case
Recurrence
55 × 30 × 25 25 × 15 × 13
17 m o 1 yr 6 m o No 3, 4 y r 10 yr No No
originated f r o m b o t h epithelial and m y o e p i t h e l i a l cells of the intercalated duct. Some studies have reported t h a t t h e i n t e r c a l a t e d d u c t i n t h e m i n o r salivary g l a n d is l a c k i n g o r s h o r t e r t h a n t h a t i n t h e p a r o t i d g l a n d . 22 T h e r e f o r e , t h i s m a y e x p l a i n w h y m o s t EMCs o c c u r i n t h e m a j o r s a l i v a r y g l a n d s . H o w e v e r , it is u n k n o w n w h y EMCs o c c u r m o r e c o m m o n l y i n t h e p a r o t i d g l a n d than the submandibular gland. This difference may be r e l a t e d t o v a r i a t i o n s in t h e i n t e r c a l a t e d d u c t s i n t h e 2 sites. Fonseca and Soares6 showed exists between
that no correlation
t h e p r o g n o s i s o f EMC a n d n e u r a l
invasion or necrosis. However,
they reported
that
cases w i t h p o o r p r o g n o s i s s h o w e d solid clear cell g r o w t h o r n u c l e a r a t y p i a in m o r e t h a n 20% o f t h e t u m o r cells. T h e r e f o r e , a c c o r d i n g t o t h e m i c r o s c o p i c findings, the
current
case
is c o n s i d e r e d
to
have
low-grade malignant potential, and a relatively good p r o g n o s i s is a n t i c i p a t e d . T h i s p a t i e n t h a s n o t s h o w n any local r e c u r r e n c e or distant metastasis for 3 years s i n c e t h e s u r g i c a l o p e r a t i o n . H o w e v e r , EMC b e h a v e s as a m a l i g n a n t n e o p l a s m , a n d a c a s e t h a t r e c u r r e d 28 y e a r s a f t e r s u r g e r y h a s b e e n r e p o r t e d . 10 T h e r e f o r e , t h e current case requires careful follow-up.
References 1. Ellis GL, Auclair PL: Tumors of the salivary glands: Atlas of Tumor Pathology, 3rd series, Fascicle 17. Washington, DC, Armed Forces Institute of Pathology, 1995, pp 228-238, 268-281 2. Seifert G, Sobin LH: Epithelial-myoepithelial carcinoma. World Health Organization International Histological Classification of Tumours: Histological Typing of Salivary Gland Tumours (ed 2). Berlin, Springer-Verlag, 1991, pp 23-24 3. Toida M, Shimokawa K: Epithelial-myoepithelial carcinoma of the parotid gland: Report of a case. J Oral Maxillofac Surg 53:476, 1995 4. Hamper K, Briigmann M, Koppermann R, et al: Epithelialmyoepithelial duct carcinoma of salivary glands: A follow-up and cytophotometric study of 21 cases. J Oral Pathol Med 18:299, 1989 5. Simpson RHW, Clarke TJ, Sarsfield PTL, et al: Epithelialmyoepithelial carcinoma of salivary glands. J Clin Pathol 44: 419, 1991
Metastasis None Supraclavicular l y m p h n o d e None None None None None
GLAND
Outcome
Alive n o disease
Alive w i t h disease Alive n o disease
6. Fonseca I, Soares J: Epithelial-myoepithelial carcinoma of the salivary glands: A study of 22 cases. Virchows Arch A Pathol Anat Histopatho1422:389, 1993 7. Donath K, Seifert G, Schmitz R: Zur diagnose und ultrastruktur des tubuliiren speichelgangkarzinoms: Epithelial-myoepitheliales schaltstiickkarzinom. Virchows Arch A Pathol Anat Histopatho1356:16, 1972 8. Noel S, BroznaJP: Epithelial-myoepithelial carcinoma ofsalivary gland with metastasis to lung: Report of a case and review of the literature. Head Neck 14:401, 1992 9. Aora VK, Misra K, Bhatia A: Cytomorphologic features of the rare epithelial-myoepithelial carcinoma of the salivary gland. Acta Cytol 34:239, 1990 10. Corio ILL,SciubbaJJ, Brannon RB, et al: Epithelial-myoepithelial carcinoma of intercalated duct origin. Oral Surg 53:280, 1982 11. Tralongo V, Daniele E: Epithelial-myoepithelial carcinoma of the salivary glands: A review of literature. Anticancer Res 18:603, 1998 12. Morrow TA, Chun T, Mirani N: Epithelial myoepithelial carcinoma of the parotid gland. Ear Nose Throat J 69:646, 1990 13. Carrillo R, Pobler E, Rocamora A, et al: Epithelial-myoepithelial carcinoma of the salivary gland: Fine needle aspiration cytologic findings. Acta Cyto134:243, 1990 14. Lampe H, Ruby RRF, Greenway RE, et al: Epithelial-myoepithelial carcinoma of the salivary gland. J Otolaryngol 13:247, 1984 15. Witterick IJ, Noyek AM, Chapnik JS, et al: Observations on the natural history of a parotid epithelial-myoepithelial carcinoma of intercalated ducts. J Otolaryngo122:176, 1993 16. Di Palma S: Epithelial-myoepithelial carcinoma with co-existing multifocal intercalated duct hyperplasia of the parotid gland. Histopathology 25:494, 1994 17. Stewart CJR, Hamilton S, Brown IL, et al: Salivary epithelialmyoepithelial carcinoma: Report of a case misinterpreted as pleomorphic adenoma on fine needle aspiration (FNA). Cytopathology 8:203, 1997 18. Morinaga S, Hashimoto S, Tezuka F: Epithelial-myoepithelial carcinoma of the parotid gland in a child. Acta Pathol Jpn 42:358, 1992 19. Stiernberg CM, Batsakis JG, Bailey BJ, et al: Epithelialmyoepithelial carcinoma of the parotid gland. Otolaryngol Head Neck Surg 94:240, 1986 20. Tralongo V, Rodolico V, Nagar C, et al: Epithelial-myoepithelial carcinoma of the salivary glands: A clinicopathologic, immunohistochemical and DNA flow cytometric study of three cases. Anticancer Res 17:761, 1997 21. Cho KJ, El-Naggar AK, Ordonez NG, et al: Epithelial-myoepithelial carcinoma of salivary glands: A clinicopathologic, DNA flow cytometric, and immunohistochemical study of Ki-67 and HER-2/neu oncogene. AmJ Clin Pathol 103:432, 1995 22. Schackleford JM, Klapper CE: Structure and carbohydrate histochemistry of mammalian salivary glands. Am J Anat 111:25, 1962
Epithelial-Myoepithelial Carcinoma Arising in the Submandibular Gland: A Case Report With I m m u n o h i s t o c h e m i c a l Study Hiroyuki Kaneko, DDS, PhD, * Takashi Muramatsu, DDS, ehO, t Hideki Ogiuchi, DDS, PhD,¢ and Masaki Shimono, DDS, PhD~ E p i t h e l i a l - m y o e p i t h e l i a l c a r c i n o m a (EMC) is a r a r e m a l i g n a n t t u m o r , w h i c h c o n s t i t u t e s a p p r o x i m a t e l y 1% o f all salivary g l a n d t u m o r s . 1 T h i s t u m o r w a s establ i s h e d as a d i s t i n c t c l i n i c o p a t h o l o g i c e n t i t y b y t h e W o r l d H e a l t h O r g a n i z a t i o n in 1991. 2 M o s t c a s e s o f EMC o c c u r p r e d o m i n a n t l y in t h e p a r o t i d g l a n d a n d s h o w a p r e d i l e c t i o n f o r f e m a l e s , w i t h a p e a k incid e n c e in t h e s e v e n t h o r e i g h t h d e c a d e o f life. 14 I n this r e p o r t , a r a r e c a s e o f EMC arising in t h e left s u b m a n d i b u l a r g l a n d in a r e l a t i v e l y y o u n g p a t i e n t is pres e n t e d . In a d d i t i o n , t h e t u m o r w a s s t u d i e d h i s t o c h e m i cally a n d i m m u n o h i s t o c h e m i c a U y .
Report of Case A 29-year-old, otherwise healthy, Japanese w o m a n was admitted to Tokyo W o m e n ' s Medical University hospital for surgical removal of a tumor on February 4, 1994. She had b e c o m e aware of slight swelling in the left submandibular region about 2 years previously and had visited a neighboring dental clinic w h e r e the submandibular swelling was attributed to pericoronitis of the left lower third molar. In January 1994, the left submandibular swelling began to gradually increase in size; therefore, she visited the hospital. The mass, measuring 2 × 1 cm, was located in the left submandibular region and was elastic hard (Fig 1). Intraoral examination indicated no swelling, redness, or disturbance
FIGURE ! • A clinical view of the tumor located in the left submandibular region.
*Assistant Professor, Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, School of Medicine, Japan. tAssistant Professor, Department of Pathology, Tokyo Dental College, Japan. ¢Professor, Department of Oral and MaxiUofacial Surgery, Tokyo Women's Medical University, School of Medicine, Japan. ]Professor, Department of Pathology, Tokyo Dental College, Japan. Address correspondence and reprint requests to Dr Kaneko: Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, School of Medicine, 8-1 Kawada-cho, ShinjukuKu, Tokyo, 162-8666 Japan; e-mail: [email protected] © 2000 American Associationof Oral and Maxillofacid Surgeons 0278-2391/00/5801-001653 0 0 / 0
FIGURE 2. A C T scan shows a high-densit~ mass in the posterior region of the left submandibular g)and (arrow). This contained highdensity areas resembling calcification (arrowhead).
98
99
KANEKO ET AL
2
3
4
5
6
7
FIGURE 3. The cut surface of the tumor shows a solid, pale-yellow mass with partially formed cyst-like spaces.
of salivary secretion. C o m p u t e d tomography s h o w e d a mass of higher density than the submandibular gland located in the posterior part of the gland. The mass had a comparatively well-defined border and the contents w e r e heterogeneous, including high-density areas of apparent calcification (Fig 2). Based on a clinical diagnosis of a benign salivary gland tumor, resection of the lesion was performed under general anesthesia on March 10, 1994. The resected s p e c i m e n measured 2.5 x 1.5 x 1.3 cm and was irregularly shaped and paie-red. The cut surface was solid and paie-yellow, with partially formed cyst-like spaces (Fig 3). She was discharged from the hospital on March 16, without any clinical symptoms.
PATHOLOGIC FINDINGS The resected tissue was fixed in 10% neutral btfffered formalin, e m b e d d e d in paraffin, and processed for routine
histologic examination. The tumor was surrounded in part by a thin fibrous capsule and c o m p o s e d of double-layered, tubule-like structures formed by inner eosinophilic ductal cells and outer clear cells, as well by solid clear cells, and spindle-shaped cells (Fig 4). Occasionally, the tumor formed solid sheets and small cysts. Solid clear cells w e r e rarer than biphasic clear cells. These clear cells had oval or polygonal cytoplasm and s h o w e d cellular polymorphism, but nuclear atypia was rarely seen. In parts of the tumor, a fibrous capsule was not present, and the clear cells invaded the adjacent submandibular gland (Fig 5). Myxoid or hyalinized stroma was occasionally observed among the tumor cells, as well as infiltration of a few inflammatory cells (Fig 6). Various-sized calcifications w e r e scattered in the stroma. For histochemical study, periodic-acid-Shift (PAS) and mucicarmine stainings w e r e used. Polyclonal keratin (PK), epithelial m e m b r a n e antigen (EMA), S-IOO protein, smooth muscle actin (HHF35), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), amylase, lactoferrin (LF), secretory c o m p o n e n t (SC), and vimentin w e r e used as primary antibodies for immunohistochemical study. These primary antibodies w e r e processed by the streptavidinbiotin (SAB) method. The inner eosinophilic cells of the tubule-like structures w e r e positive for PK, EMA, SC, and amylase (Fig 7). Clear cells that showed both solid and tubular growth reacted with S-IO0, GFAP, and vimentin (Fig 8), and had diastase-soluble PAS granules in their cytoplasm. A few solid clear cells s h o w e d positivity for HHF35. No cells positive for NSE, LF, or mucicarmine staining w e r e observed. The tumor was diagnosed as EMC arising in the submandibular gland.
Discussion EMC w a s first d e s c r i b e d b y D o n a t h et al in 1972. 7 It is g e n e r a l l y a c c e p t e d t h a t EMC w a s p r e v i o u s l y reported under a variety of names, including adenomyoepithelioma, glycogen-rich adenoma, glycogen-rich
FIGURE 4. The tumor component is composed of biphasic structures formed by inner epithelial cells and outer clear cells (HE stain, original magnification x 100).
] O0
EMC ARISING IN THE SUBMANDIBULAR GLAND
FIGURE 5. Clear tumor cells invade the adjacent submandibulargland, and the remainingacini can be observed (arrowheads) (HE stain, original magnification x 100).
c a r c i n o m a , c l e a r cell a d e n o m a , a n d c l e a r cell carcin o m a . 1,6,s,9 H o w e v e r , EMC w a s listed in t h e r e c e n t W o r l d Health O r g a n i z a t i o n classification as a distinct c l i n i c o p a t h o l o g i c entity. 2 F r o m 70% to 80% o f EMCs o c c u r in t h e p a r o t i d gland, w i t h a p r e d i l e c t i o n for females. M o r e o v e r , EMC o c c u r s p r e d o m i n a n t l y in t h e s e v e n t h o r e i g h t h d e c a d e o f life, a n d t h e m e a n age o f p a t i e n t s is a p p r o x i m a t e l y 60 years. 1-3,10 To o u r k n o w l e d g e , m o r e t h a n 140 cases o f EMC have b e e n r e p o r t e d in t h e English literature. 3,s,9,11-19 Of
t h e s e cases, 12 o c c u r r e d in t h e s u b m a n d i b u l a r gland~,5,7,9,1°,2°,21; this c o n s t i t u t e s 8.6% o f all EMC cases. T h e o c c u r r e n c e is similar to that p r e v i o u s l y r e p o r t e d . 1 T h e cases r e p o r t s o f EMC arising in t h e s u b m a n d i b u l a r g l a n d that h a d sufficient i n f o r m a t i o n are s h o w n in Table 1. A m o n g EMC cases in t h e p a r o t i d gland, 6 p a t i e n t s w e r e u n d e r 30 y e a r o f age, a n d t h e y o u n g e s t p a t i e n t w a s an 8-year-old boy. H o w e v e r , in t h e s u b m a n d i b u l a r g l a n d cases, t h e ages r a n g e d f r o m 65 to 103 years, w i t h a m e a n age o f 71 years. T h e
FIGURE 6. Myxoid and hyalinized stroma are occasionallyobserved (HE stain, original magnification x 100).
KANEKO ET AL
]0 1
FIGURE 7. The inner ductal cells are positive for polyclonal keratin (original magnification x 4 0 0 )
gender distribution was 4 males and 3 females. Therefore, the current case may be the youngest reported patient with EMC arising in the submandibular gland. Local recurrence occurred in 4 cases of EMC in the submandibular gland, but distant metastases appeared in only 1 case involving a supraclavicular lymph node. EMC is generally considered to be a low-grade malignant neoplasm that recurs frequently at local sites, but distant metastasis is extremely rare. Previous studies have shown that 40% of EMC cases have recurred at
local sites and 17% have metastasized to regional lymph nodes.l,3,5 Accordingly, the prognosis for EMC shows no differences between those arising in the submandibular gland and in other sites. Based on the immunohistochemical observations, the inner eosinophilic cells of biphasic proliferation reacted with epithelial and secretory markers, and the outer clear cells were positive for myoepithelial markers. This reactivity is similar to that previously reported. 1,4,8,9 The findings suggest that this tumor
FIGURE 8. The outer clear cells react with S 100 (original magnification x 4 0 0 )
] 02
EMC ARISING IN THE S U B M A N D I B ~
Authors
Age
Sex
Size ( m m )
Aora et al Simpson et al Cho et al
65 103 77 67 72 74 29
M F F M F M F
40 × 20 60 × 50 × 30
Tralongo et al Present case
Recurrence
55 × 30 × 25 25 × 15 × 13
17 m o 1 yr 6 m o No 3, 4 y r 10 yr No No
originated f r o m b o t h epithelial and m y o e p i t h e l i a l cells of the intercalated duct. Some studies have reported t h a t t h e i n t e r c a l a t e d d u c t i n t h e m i n o r salivary g l a n d is l a c k i n g o r s h o r t e r t h a n t h a t i n t h e p a r o t i d g l a n d . 22 T h e r e f o r e , t h i s m a y e x p l a i n w h y m o s t EMCs o c c u r i n t h e m a j o r s a l i v a r y g l a n d s . H o w e v e r , it is u n k n o w n w h y EMCs o c c u r m o r e c o m m o n l y i n t h e p a r o t i d g l a n d than the submandibular gland. This difference may be r e l a t e d t o v a r i a t i o n s in t h e i n t e r c a l a t e d d u c t s i n t h e 2 sites. Fonseca and Soares6 showed exists between
that no correlation
t h e p r o g n o s i s o f EMC a n d n e u r a l
invasion or necrosis. However,
they reported
that
cases w i t h p o o r p r o g n o s i s s h o w e d solid clear cell g r o w t h o r n u c l e a r a t y p i a in m o r e t h a n 20% o f t h e t u m o r cells. T h e r e f o r e , a c c o r d i n g t o t h e m i c r o s c o p i c findings, the
current
case
is c o n s i d e r e d
to
have
low-grade malignant potential, and a relatively good p r o g n o s i s is a n t i c i p a t e d . T h i s p a t i e n t h a s n o t s h o w n any local r e c u r r e n c e or distant metastasis for 3 years s i n c e t h e s u r g i c a l o p e r a t i o n . H o w e v e r , EMC b e h a v e s as a m a l i g n a n t n e o p l a s m , a n d a c a s e t h a t r e c u r r e d 28 y e a r s a f t e r s u r g e r y h a s b e e n r e p o r t e d . 10 T h e r e f o r e , t h e current case requires careful follow-up.
References 1. Ellis GL, Auclair PL: Tumors of the salivary glands: Atlas of Tumor Pathology, 3rd series, Fascicle 17. Washington, DC, Armed Forces Institute of Pathology, 1995, pp 228-238, 268-281 2. Seifert G, Sobin LH: Epithelial-myoepithelial carcinoma. World Health Organization International Histological Classification of Tumours: Histological Typing of Salivary Gland Tumours (ed 2). Berlin, Springer-Verlag, 1991, pp 23-24 3. Toida M, Shimokawa K: Epithelial-myoepithelial carcinoma of the parotid gland: Report of a case. J Oral Maxillofac Surg 53:476, 1995 4. Hamper K, Briigmann M, Koppermann R, et al: Epithelialmyoepithelial duct carcinoma of salivary glands: A follow-up and cytophotometric study of 21 cases. J Oral Pathol Med 18:299, 1989 5. Simpson RHW, Clarke TJ, Sarsfield PTL, et al: Epithelialmyoepithelial carcinoma of salivary glands. J Clin Pathol 44: 419, 1991
Metastasis None Supraclavicular l y m p h n o d e None None None None None
GLAND
Outcome
Alive n o disease
Alive w i t h disease Alive n o disease
6. Fonseca I, Soares J: Epithelial-myoepithelial carcinoma of the salivary glands: A study of 22 cases. Virchows Arch A Pathol Anat Histopatho1422:389, 1993 7. Donath K, Seifert G, Schmitz R: Zur diagnose und ultrastruktur des tubuliiren speichelgangkarzinoms: Epithelial-myoepitheliales schaltstiickkarzinom. Virchows Arch A Pathol Anat Histopatho1356:16, 1972 8. Noel S, BroznaJP: Epithelial-myoepithelial carcinoma ofsalivary gland with metastasis to lung: Report of a case and review of the literature. Head Neck 14:401, 1992 9. Aora VK, Misra K, Bhatia A: Cytomorphologic features of the rare epithelial-myoepithelial carcinoma of the salivary gland. Acta Cytol 34:239, 1990 10. Corio ILL,SciubbaJJ, Brannon RB, et al: Epithelial-myoepithelial carcinoma of intercalated duct origin. Oral Surg 53:280, 1982 11. Tralongo V, Daniele E: Epithelial-myoepithelial carcinoma of the salivary glands: A review of literature. Anticancer Res 18:603, 1998 12. Morrow TA, Chun T, Mirani N: Epithelial myoepithelial carcinoma of the parotid gland. Ear Nose Throat J 69:646, 1990 13. Carrillo R, Pobler E, Rocamora A, et al: Epithelial-myoepithelial carcinoma of the salivary gland: Fine needle aspiration cytologic findings. Acta Cyto134:243, 1990 14. Lampe H, Ruby RRF, Greenway RE, et al: Epithelial-myoepithelial carcinoma of the salivary gland. J Otolaryngol 13:247, 1984 15. Witterick IJ, Noyek AM, Chapnik JS, et al: Observations on the natural history of a parotid epithelial-myoepithelial carcinoma of intercalated ducts. J Otolaryngo122:176, 1993 16. Di Palma S: Epithelial-myoepithelial carcinoma with co-existing multifocal intercalated duct hyperplasia of the parotid gland. Histopathology 25:494, 1994 17. Stewart CJR, Hamilton S, Brown IL, et al: Salivary epithelialmyoepithelial carcinoma: Report of a case misinterpreted as pleomorphic adenoma on fine needle aspiration (FNA). Cytopathology 8:203, 1997 18. Morinaga S, Hashimoto S, Tezuka F: Epithelial-myoepithelial carcinoma of the parotid gland in a child. Acta Pathol Jpn 42:358, 1992 19. Stiernberg CM, Batsakis JG, Bailey BJ, et al: Epithelialmyoepithelial carcinoma of the parotid gland. Otolaryngol Head Neck Surg 94:240, 1986 20. Tralongo V, Rodolico V, Nagar C, et al: Epithelial-myoepithelial carcinoma of the salivary glands: A clinicopathologic, immunohistochemical and DNA flow cytometric study of three cases. Anticancer Res 17:761, 1997 21. Cho KJ, El-Naggar AK, Ordonez NG, et al: Epithelial-myoepithelial carcinoma of salivary glands: A clinicopathologic, DNA flow cytometric, and immunohistochemical study of Ki-67 and HER-2/neu oncogene. AmJ Clin Pathol 103:432, 1995 22. Schackleford JM, Klapper CE: Structure and carbohydrate histochemistry of mammalian salivary glands. Am J Anat 111:25, 1962