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Mucoepidermoid carcinoma of the lacrimal sac
CYTOLOGIC-PATHOLOGIC CORRELATION
Mucoepidermoid Carcinoma of the Lacrimal Sac JoAnna D. Williams, MD, Amit Agrawal, MD, and Paul E. Wakely, Jr, MD Mucoepidermoid carcinoma of the lacrimal sac is a rare entity. We report a case of mucoepidermoid carcinoma arising in the lacrimal sac of a 30-year-old man who presented with an inner canthal mass. To our knowledge this is the first example of the cytopathology of this neoplasm in this anatomic site. Ann Diagn Pathol 7: 31-34, 2003. Copyright 2003, Elsevier Science (USA). All rights reserved. Index Words: Mucoepidermoid carcinoma, lacrimal sac, fine needle aspiration
M
UCOEPIDERMOID carcinoma (MEC) is the most common malignant salivary gland tumor and accounts for 5% of all salivary gland neoplasms.1 Mucoepidermoid carcinoma has been reported in other locations including the larynx, trachea, bronchi, nasal mucosa, maxilla, mandible, thymus, esophagus, breast, liver, uterine cervix, penis, anus, conjunctiva, lacrimal gland, and lacrimal sac.2-12 Unlike the salivary gland, MEC of the lacrimal sac is rare, with only eight previously reported cases.12-16 We report an example correlating the fine needle aspiration (FNA) cytopathology and histopathology of lacrimal sac MEC. Case Report A 30-year-old white man was referred to the otolaryngology clinic with a 2-year history of a slow-growing 1.3 cm left medial canthal nodule, which he initially noticed after an insect bite to the area. He was also experiencing epiphora of the left eye, but denied pain or visual changes. His past medical history was otherwise unremarkable. Visual acuity was 20/20 in both eyes. Intraocular pressure, funduscopic exam, and ocular motility were also normal. An FNA biopsy performed at another institution 1 year before referral was consistent with a benign dacryocystocele. Radiologic studies at that time revealed a solid lesion with no involvement of bone. Upon referral to our clinic, a repeat FNA was performed. Irrigation of the left nasal lacrimal outflow system was attempted; however, the duct was obstructed. The pa-
From the Departments of Pathology and Otolaryngology, The Ohio State University College of Medicine, Columbus, OH. Address reprint requests to Paul E. Wakely, Jr, MD, Department of Pathology, 414 Doan Hall, 410 West 10th Ave, Columbus, OH 43210. Copyright 2003, Elsevier Science (USA). All rights reserved. 1092-9134/03/0701-0006$35.00/0 doi:10.1053/adpa.2003.50005
tient underwent excisional biopsy and subsequent partial facial skin resection, partial maxillectomy, ethmoidectomy, sphenoid sinusotomy, medial canthoplasty, and local flap reconstruction. The patient received adjuvant radiation therapy because of positive soft tissue margins. He is currently free of disease 1 year later.
Cytologic Findings Smears from the second FNA consisted predominantly of thick strands and microfragments of mucus with only scattered small cell clusters and cellular debris (Fig 1). Cell aggregates were composed of cytologically bland, medium-sized “intermediate” cells with slightly enlarged uniform nuclei, indistinct nucleoli (best seen on the Papanicolaou stain) and a moderate amount of cytoplasm (Fig 2). Although true goblet cells were not appreciated, many banal-appearing ciliated columnar cells could be seen in the mucinous background either as single forms or in loose groupings. (Fig 3). Factors that would favor a malignancy such as necrosis, atypical squamous cells with or without keratinization, anisonucleosis or marked nucleomegaly, and prominent nucleoli were absent from smears. Because of the absence of overt malignant cytologic features, and since the lacrimal sac is normally lined by ciliated epithelium and even goblet cells, the aspirate was signed out as consistent with a benign mucinous lesion.
Gross and Histologic Findings The patient underwent partial excision of the lesion. Hematoxylin-eosin–stained tissue sections revealed an invasive low-grade MEC, extending to tissue edges. Histologically, cystic, mucin-filled, rounded-to-angulated cell islands lined by goblet cells, columnar cells (some which were ciliated), and intermediate cells haphazardly infiltrated the fibro-inflammatory stroma (Fig 4). Nearly acellular pools of mucin dissected into the stroma in areas. The biopsy was sent for a second opinion and a diagnosis of MEC was confirmed. The patient subse-
Annals of Diagnostic Pathology, Vol 7, No 1 (February), 2003: pp 31-34
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Figure 1. (A) Two tightly clustered cell aggregates are adjacent to several large densely opaque fragments of mucin. (Romanowsky stain; scanning magnification.) (B) Polygonal and columnar cells are embedded within strands of mucus which has a “stringy” appearance. (Papanicolaou stain; scanning magnification.)
quently underwent complete tumor resection, which included portions of the left maxilla, left lacrimal fossa, left orbital rim, and facial soft tissue. Residual low-grade MEC was present with mucinous cysts. Soft tissue margins were positive for carcinoma.
Discussion The lacrimal sac is located in the superomedial canthal region and is normally not palpable. Malignant tumors arising in this region are mainly carcinomas including MEC.16 Mucoepidermoid carcinoma presents as a slowgrowing, mobile mass in most anatomic sites. Average age at onset is 40 to 55 years, with a slight female predominance.17 Cytologic and histologic
Figure 2. Polygonal intermediate-type cells have uniformly sized rounded nuclei and a moderate amount of nondescript cytoplasm. Note the absence of vacuolization. (Romanowsky stain; High-power magnification.)
variation is characteristic of this tumor, and a source of diagnostic difficulty. Diagnosis of MEC by FNA biopsy typically requires the coexistence of three cell types: epidermoid cells, intermediate cells, and mucin-secreting cells.1 However, it is quite frequent that all three cell elements are not present in aspirates, thus explaining the low diagnostic rates identified in various FNA series of MEC.18 A diagnostic accuracy of only 37% was reported by Zajicek et al.19 In a series of 50 cases of MEC having both cytology and histology available for examination, a malignant diagnosis was suspected in only 68% of cases eventually proven to be low-grade MEC, while the cytologic diagnosis of intermediate- or high-grade MEC was higher (87%).17 Kumar et al18 expressed the main reasons for diagnostic failure in MEC were either the absence of cytologic atypia or inadequacy of cellular material in the aspirate. Both of these factors contributed to a mistaken FNA diagnosis of benignancy in our case. These authors proposed that the presence of mucoid material and mucus-producing cells in a benign-appearing tumor should always raise the suspicion of well-differentiated MEC. Smears from low-grade MEC have a background of mucus and debris with cohesive cell clusters and flat sheets of cells as well as short skeins of cells within mucus. Mucus-producing cells may be loosely cohesive and vacuolated resembling histiocytes. True squamous differentiation with cytoplasmic keratinization and nucleoli are much more characteristic of high-grade MEC.1 Cohen et al20 evaluated 13 cytologic features in 34 cases of MEC
MEC of the Lacrimal Sac
33
Figure 3. Singly dispersed banal-appearing columnar cells contain well-developed cilia, adding to the false impression of a benign lesion. (A) Papanicolaou stain; high-power magnification. (B) Romanowsky stain; High-power magnification.
including overlapping epithelial groups, mucincontaining cells, intermediate cells, squamous cells, clusters of finely vacuolated cells, extracellular mucin, prominent nucleoli, nuclear atypia, glandular structures, foamy macrophages, lymphocytes, necrosis, and fibrous tissue. Through regression analysis they found that, when seen together, three morphologic features (intermediate cells, squamous cells, and overlapping epithelial groups) had a sensitivity and specificity of 97% and 100%, respectively, for recognizing MEC. Their findings differ from most reports by not including mucinsecreting cells or background mucin as key morphologic features. Using their criteria it would still have been difficult to render a definitive diagnosis of MEC in our patient because smears not only
lacked clear cut squamous cells, but instead contained many ciliated cells. Ciliated cells (a morphologic feature that strongly implicates a benign process in both tissue sections and aspirates) are extremely unusual in any type of carcinoma. They have only rarely been described as part of the histopathologic findings of MEC.21 Yet such cells were seen as part of the lining of the malignant glands and infiltrating mucin pools in tissue sections of this example of MEC. One could argue that these ciliated cells represented residual lacrimal sac epithelium, but such cells were incorporated into the cellular composition of malignant glands. Neoplasms that enter the differential diagnosis of low-grade MEC on aspirates include acinic cell carcinoma, Warthin’s tumor, cystadenoma, and
Figure 4. (A) Cell islands with irregular borders show a haphazard pattern of infiltration within a fibrous and inflammatory stroma. Extracellular mucin is seen in some of these cell nests, which are lined by intermediate cells, occasional ciliated cells, and mucin-secreting columnar cells. (B) A cluster of ciliated columnar cells is set in an extravasated infiltrating mucin pool. (High-power magnification.)
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cystadenocarcinoma.1 The combination of abundant mucin and intermediate-type cells is typically absent from smears of these entities. Non-neoplastic entities such as retention cysts, simple cysts, and inflammatory processes may also have mucus, debris, metaplastic cells, and glandular cells. Histopathology of low-grade MEC consists primarily of intermediate cells in solid nests and as glands containing variable numbers of mucus-producing goblet cells, small numbers of epidermoid cells, and intraluminal mucin or extravasated pools of mucin seemingly devoid of cells. Mucus-forming cells may be singly dispersed among columnar or clear cells or arranged in small clusters intermingled with the nests of intermediate cells. Extravasated mucus may induce a foreign body giant cell reaction, which could also contribute to a confusing picture on aspirate smears. Goode et al22 described a histologic grading system for MEC by assigning point values to five criteria: intracystic component ⬍20% (⫹2); neural invasion present (⫹2); necrosis (⫹3); mitosis, 4 or more per high power field (⫹3); and anaplasia (⫹4). Scores of 0 to 4 are considered low grade, 5 to 6 intermediate grade, and 7 to 14 high grade. Because our case lacked neural invasion, necrosis greater than 4 mitoses per high power field, and anaplasia, the tumor was classified as low grade. Low-grade MEC rarely metastasizes; however, local recurrence is common if the tumor is not completely excised. Treatment is typically wide excision with postoperative radiation therapy if soft tissue margins are positive as in our patient. Mucoepidermoid carcinoma should be considered in FNAs of a mass lesion from the lacrimal sac when abundant mucin and epithelial cells (regardless of whether they are ciliated or not) are present. Definitive cytologic diagnosis requires a high degree of suspicion. References 1. Orell SR, Sterrett GF, Walters MN-I, et al: Head and neck salivary glands, in Orell SR (ed): Manual and Atlas of Fine Needle Aspiration Cytology (ed 3). London, Churchill Livingstone, 2001, pp 40-72 2. Heilbrunn A, Crosby IK: Adenocystic carcinoma and mucoepidermoid carcinoma of the tracheobronchial tree. Chest 1972;91:145-149 3. Hampert H, Hellweg G: On mucoepidermoid tumors of different sites. Cancer 1957;10:1187-1192
4. Costoyas NR, Muller EM, Marfort A, et al: Tumor mucoepidermoid de maxillar superior. Rev Assoc Odontol Argent 1969;57:86-88 5. Bhaskar SN: Central mucoepidermoid tumor of the mandible. Cancer 1963;16:721-726 6. Snover DC, Levine GD, Rosai J: Thymic carcinoma. Five distinct histologic variants. Am J Surg Pathol 1982;6:451-470 7. Weitzner S: Mucoepidermoid carcinoma of the esophagus. Arch Pathol Lab Med 1970;90:271-280 8. Patchefsky AS, Frauenhoffer CM, Krall RA, et al: Low-grade mucoepidermoid carcinoma of the breast. Arch Pathol Lab Med 1979;103:196-198 9. Pianzola LE, Drut R: Mucoepidermoid carcinoma of the liver. Am J Clin Pathol 1971;56:258-261 10. Shrikhande SW, Sirsat MW: Mucoepidermoid carcinoma of the penis: Report of an unusual case. Br J Urol 1974;46:233235 11. Paulino AFG, Huvos AG: Epithelial tumors of the lacrimal glands: A clinicopathologic study. Ann Diagn Pathol 1999;3:199204 12. Bambirra EA, Miranda D, Rayes A: Mucoepidermoid tumor of the lacrimal sac. Arch Ophthalmol 1981;99:2149-2150 13. Fliss DM, Freeman JL, Hurwitz JJ, et al: Mucoepidermoid carcinoma of the lacrimal sac: A report of two cases, with observations on the histogenesis. Can J Ophthalmol 1993;28: 228-235 14. Khan JA, Sutula FC, Pilch BZ, et al: Mucoepidermoid carcinoma involving the lacrimal sac. Ophthal Plast Reconstr Surg 1988;4:153-157 15. Blake J, Mullaney J, Gillan J: Lacrimal sac mucoepidermoid carcinoma. Br J Ophthalmol 1986;70:681-685 16. Ni C, Wagoner MD, Wang W, et al: Mucoepidermoid carcinomas of the lacrimal sac. Arch Ophthalmol 1983;101: 1572-1574 17. Klijanienko J, Vielh P: Fine-needle sampling of salivary gland lesions IV. Review of 50 cases of mucoepidermoid carcinoma with histologic correlation. Diagn Cytopathol 1997;17: 92-98 18. Kumar N, Kapila K, Verma K: Fine needle aspiration cytology of mucoepidermoid carcinoma. A diagnostic problem. Acta Cytol 1991;35:357-359 19. Zajicek J, Eneroth CM, Jacobson P: Aspiration biopsy of salivary gland tumors: IV. Morphologic studies on smears and histologic sections from mucoepidermoid carcinoma. Acta Cytol 1976;20:35-41 20. Cohen MB, Fisher PE, Holly EA, et al: Fine needle aspiration biopsy diagnosis of mucoepidermoid carcinoma, statistical analysis. Acta Cytol 1990;34:43-49 21. Wenig B, Adair CF, Heffess CS: Primary mucoepidermoid carcinoma of the thyroid gland: A report of six cases and a review of the literature of a follicular epithelial-derived tumor. Hum Pathol 1995;26:1099-1108 22. Goode RK, Auclair PL, Ellis GL: Mucoepidermoid carcinoma of the major salivary glands. Clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 1998;82:1217-1224
Mucoepidermoid Carcinoma of the Lacrimal Sac JoAnna D. Williams, MD, Amit Agrawal, MD, and Paul E. Wakely, Jr, MD Mucoepidermoid carcinoma of the lacrimal sac is a rare entity. We report a case of mucoepidermoid carcinoma arising in the lacrimal sac of a 30-year-old man who presented with an inner canthal mass. To our knowledge this is the first example of the cytopathology of this neoplasm in this anatomic site. Ann Diagn Pathol 7: 31-34, 2003. Copyright 2003, Elsevier Science (USA). All rights reserved. Index Words: Mucoepidermoid carcinoma, lacrimal sac, fine needle aspiration
M
UCOEPIDERMOID carcinoma (MEC) is the most common malignant salivary gland tumor and accounts for 5% of all salivary gland neoplasms.1 Mucoepidermoid carcinoma has been reported in other locations including the larynx, trachea, bronchi, nasal mucosa, maxilla, mandible, thymus, esophagus, breast, liver, uterine cervix, penis, anus, conjunctiva, lacrimal gland, and lacrimal sac.2-12 Unlike the salivary gland, MEC of the lacrimal sac is rare, with only eight previously reported cases.12-16 We report an example correlating the fine needle aspiration (FNA) cytopathology and histopathology of lacrimal sac MEC. Case Report A 30-year-old white man was referred to the otolaryngology clinic with a 2-year history of a slow-growing 1.3 cm left medial canthal nodule, which he initially noticed after an insect bite to the area. He was also experiencing epiphora of the left eye, but denied pain or visual changes. His past medical history was otherwise unremarkable. Visual acuity was 20/20 in both eyes. Intraocular pressure, funduscopic exam, and ocular motility were also normal. An FNA biopsy performed at another institution 1 year before referral was consistent with a benign dacryocystocele. Radiologic studies at that time revealed a solid lesion with no involvement of bone. Upon referral to our clinic, a repeat FNA was performed. Irrigation of the left nasal lacrimal outflow system was attempted; however, the duct was obstructed. The pa-
From the Departments of Pathology and Otolaryngology, The Ohio State University College of Medicine, Columbus, OH. Address reprint requests to Paul E. Wakely, Jr, MD, Department of Pathology, 414 Doan Hall, 410 West 10th Ave, Columbus, OH 43210. Copyright 2003, Elsevier Science (USA). All rights reserved. 1092-9134/03/0701-0006$35.00/0 doi:10.1053/adpa.2003.50005
tient underwent excisional biopsy and subsequent partial facial skin resection, partial maxillectomy, ethmoidectomy, sphenoid sinusotomy, medial canthoplasty, and local flap reconstruction. The patient received adjuvant radiation therapy because of positive soft tissue margins. He is currently free of disease 1 year later.
Cytologic Findings Smears from the second FNA consisted predominantly of thick strands and microfragments of mucus with only scattered small cell clusters and cellular debris (Fig 1). Cell aggregates were composed of cytologically bland, medium-sized “intermediate” cells with slightly enlarged uniform nuclei, indistinct nucleoli (best seen on the Papanicolaou stain) and a moderate amount of cytoplasm (Fig 2). Although true goblet cells were not appreciated, many banal-appearing ciliated columnar cells could be seen in the mucinous background either as single forms or in loose groupings. (Fig 3). Factors that would favor a malignancy such as necrosis, atypical squamous cells with or without keratinization, anisonucleosis or marked nucleomegaly, and prominent nucleoli were absent from smears. Because of the absence of overt malignant cytologic features, and since the lacrimal sac is normally lined by ciliated epithelium and even goblet cells, the aspirate was signed out as consistent with a benign mucinous lesion.
Gross and Histologic Findings The patient underwent partial excision of the lesion. Hematoxylin-eosin–stained tissue sections revealed an invasive low-grade MEC, extending to tissue edges. Histologically, cystic, mucin-filled, rounded-to-angulated cell islands lined by goblet cells, columnar cells (some which were ciliated), and intermediate cells haphazardly infiltrated the fibro-inflammatory stroma (Fig 4). Nearly acellular pools of mucin dissected into the stroma in areas. The biopsy was sent for a second opinion and a diagnosis of MEC was confirmed. The patient subse-
Annals of Diagnostic Pathology, Vol 7, No 1 (February), 2003: pp 31-34
31
32
Williams, Agrawal, and Wakely
Figure 1. (A) Two tightly clustered cell aggregates are adjacent to several large densely opaque fragments of mucin. (Romanowsky stain; scanning magnification.) (B) Polygonal and columnar cells are embedded within strands of mucus which has a “stringy” appearance. (Papanicolaou stain; scanning magnification.)
quently underwent complete tumor resection, which included portions of the left maxilla, left lacrimal fossa, left orbital rim, and facial soft tissue. Residual low-grade MEC was present with mucinous cysts. Soft tissue margins were positive for carcinoma.
Discussion The lacrimal sac is located in the superomedial canthal region and is normally not palpable. Malignant tumors arising in this region are mainly carcinomas including MEC.16 Mucoepidermoid carcinoma presents as a slowgrowing, mobile mass in most anatomic sites. Average age at onset is 40 to 55 years, with a slight female predominance.17 Cytologic and histologic
Figure 2. Polygonal intermediate-type cells have uniformly sized rounded nuclei and a moderate amount of nondescript cytoplasm. Note the absence of vacuolization. (Romanowsky stain; High-power magnification.)
variation is characteristic of this tumor, and a source of diagnostic difficulty. Diagnosis of MEC by FNA biopsy typically requires the coexistence of three cell types: epidermoid cells, intermediate cells, and mucin-secreting cells.1 However, it is quite frequent that all three cell elements are not present in aspirates, thus explaining the low diagnostic rates identified in various FNA series of MEC.18 A diagnostic accuracy of only 37% was reported by Zajicek et al.19 In a series of 50 cases of MEC having both cytology and histology available for examination, a malignant diagnosis was suspected in only 68% of cases eventually proven to be low-grade MEC, while the cytologic diagnosis of intermediate- or high-grade MEC was higher (87%).17 Kumar et al18 expressed the main reasons for diagnostic failure in MEC were either the absence of cytologic atypia or inadequacy of cellular material in the aspirate. Both of these factors contributed to a mistaken FNA diagnosis of benignancy in our case. These authors proposed that the presence of mucoid material and mucus-producing cells in a benign-appearing tumor should always raise the suspicion of well-differentiated MEC. Smears from low-grade MEC have a background of mucus and debris with cohesive cell clusters and flat sheets of cells as well as short skeins of cells within mucus. Mucus-producing cells may be loosely cohesive and vacuolated resembling histiocytes. True squamous differentiation with cytoplasmic keratinization and nucleoli are much more characteristic of high-grade MEC.1 Cohen et al20 evaluated 13 cytologic features in 34 cases of MEC
MEC of the Lacrimal Sac
33
Figure 3. Singly dispersed banal-appearing columnar cells contain well-developed cilia, adding to the false impression of a benign lesion. (A) Papanicolaou stain; high-power magnification. (B) Romanowsky stain; High-power magnification.
including overlapping epithelial groups, mucincontaining cells, intermediate cells, squamous cells, clusters of finely vacuolated cells, extracellular mucin, prominent nucleoli, nuclear atypia, glandular structures, foamy macrophages, lymphocytes, necrosis, and fibrous tissue. Through regression analysis they found that, when seen together, three morphologic features (intermediate cells, squamous cells, and overlapping epithelial groups) had a sensitivity and specificity of 97% and 100%, respectively, for recognizing MEC. Their findings differ from most reports by not including mucinsecreting cells or background mucin as key morphologic features. Using their criteria it would still have been difficult to render a definitive diagnosis of MEC in our patient because smears not only
lacked clear cut squamous cells, but instead contained many ciliated cells. Ciliated cells (a morphologic feature that strongly implicates a benign process in both tissue sections and aspirates) are extremely unusual in any type of carcinoma. They have only rarely been described as part of the histopathologic findings of MEC.21 Yet such cells were seen as part of the lining of the malignant glands and infiltrating mucin pools in tissue sections of this example of MEC. One could argue that these ciliated cells represented residual lacrimal sac epithelium, but such cells were incorporated into the cellular composition of malignant glands. Neoplasms that enter the differential diagnosis of low-grade MEC on aspirates include acinic cell carcinoma, Warthin’s tumor, cystadenoma, and
Figure 4. (A) Cell islands with irregular borders show a haphazard pattern of infiltration within a fibrous and inflammatory stroma. Extracellular mucin is seen in some of these cell nests, which are lined by intermediate cells, occasional ciliated cells, and mucin-secreting columnar cells. (B) A cluster of ciliated columnar cells is set in an extravasated infiltrating mucin pool. (High-power magnification.)
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cystadenocarcinoma.1 The combination of abundant mucin and intermediate-type cells is typically absent from smears of these entities. Non-neoplastic entities such as retention cysts, simple cysts, and inflammatory processes may also have mucus, debris, metaplastic cells, and glandular cells. Histopathology of low-grade MEC consists primarily of intermediate cells in solid nests and as glands containing variable numbers of mucus-producing goblet cells, small numbers of epidermoid cells, and intraluminal mucin or extravasated pools of mucin seemingly devoid of cells. Mucus-forming cells may be singly dispersed among columnar or clear cells or arranged in small clusters intermingled with the nests of intermediate cells. Extravasated mucus may induce a foreign body giant cell reaction, which could also contribute to a confusing picture on aspirate smears. Goode et al22 described a histologic grading system for MEC by assigning point values to five criteria: intracystic component ⬍20% (⫹2); neural invasion present (⫹2); necrosis (⫹3); mitosis, 4 or more per high power field (⫹3); and anaplasia (⫹4). Scores of 0 to 4 are considered low grade, 5 to 6 intermediate grade, and 7 to 14 high grade. Because our case lacked neural invasion, necrosis greater than 4 mitoses per high power field, and anaplasia, the tumor was classified as low grade. Low-grade MEC rarely metastasizes; however, local recurrence is common if the tumor is not completely excised. Treatment is typically wide excision with postoperative radiation therapy if soft tissue margins are positive as in our patient. Mucoepidermoid carcinoma should be considered in FNAs of a mass lesion from the lacrimal sac when abundant mucin and epithelial cells (regardless of whether they are ciliated or not) are present. Definitive cytologic diagnosis requires a high degree of suspicion. References 1. Orell SR, Sterrett GF, Walters MN-I, et al: Head and neck salivary glands, in Orell SR (ed): Manual and Atlas of Fine Needle Aspiration Cytology (ed 3). London, Churchill Livingstone, 2001, pp 40-72 2. Heilbrunn A, Crosby IK: Adenocystic carcinoma and mucoepidermoid carcinoma of the tracheobronchial tree. Chest 1972;91:145-149 3. Hampert H, Hellweg G: On mucoepidermoid tumors of different sites. Cancer 1957;10:1187-1192
4. Costoyas NR, Muller EM, Marfort A, et al: Tumor mucoepidermoid de maxillar superior. Rev Assoc Odontol Argent 1969;57:86-88 5. Bhaskar SN: Central mucoepidermoid tumor of the mandible. Cancer 1963;16:721-726 6. Snover DC, Levine GD, Rosai J: Thymic carcinoma. Five distinct histologic variants. Am J Surg Pathol 1982;6:451-470 7. Weitzner S: Mucoepidermoid carcinoma of the esophagus. Arch Pathol Lab Med 1970;90:271-280 8. Patchefsky AS, Frauenhoffer CM, Krall RA, et al: Low-grade mucoepidermoid carcinoma of the breast. Arch Pathol Lab Med 1979;103:196-198 9. Pianzola LE, Drut R: Mucoepidermoid carcinoma of the liver. Am J Clin Pathol 1971;56:258-261 10. Shrikhande SW, Sirsat MW: Mucoepidermoid carcinoma of the penis: Report of an unusual case. Br J Urol 1974;46:233235 11. Paulino AFG, Huvos AG: Epithelial tumors of the lacrimal glands: A clinicopathologic study. Ann Diagn Pathol 1999;3:199204 12. Bambirra EA, Miranda D, Rayes A: Mucoepidermoid tumor of the lacrimal sac. Arch Ophthalmol 1981;99:2149-2150 13. Fliss DM, Freeman JL, Hurwitz JJ, et al: Mucoepidermoid carcinoma of the lacrimal sac: A report of two cases, with observations on the histogenesis. Can J Ophthalmol 1993;28: 228-235 14. Khan JA, Sutula FC, Pilch BZ, et al: Mucoepidermoid carcinoma involving the lacrimal sac. Ophthal Plast Reconstr Surg 1988;4:153-157 15. Blake J, Mullaney J, Gillan J: Lacrimal sac mucoepidermoid carcinoma. Br J Ophthalmol 1986;70:681-685 16. Ni C, Wagoner MD, Wang W, et al: Mucoepidermoid carcinomas of the lacrimal sac. Arch Ophthalmol 1983;101: 1572-1574 17. Klijanienko J, Vielh P: Fine-needle sampling of salivary gland lesions IV. Review of 50 cases of mucoepidermoid carcinoma with histologic correlation. Diagn Cytopathol 1997;17: 92-98 18. Kumar N, Kapila K, Verma K: Fine needle aspiration cytology of mucoepidermoid carcinoma. A diagnostic problem. Acta Cytol 1991;35:357-359 19. Zajicek J, Eneroth CM, Jacobson P: Aspiration biopsy of salivary gland tumors: IV. Morphologic studies on smears and histologic sections from mucoepidermoid carcinoma. Acta Cytol 1976;20:35-41 20. Cohen MB, Fisher PE, Holly EA, et al: Fine needle aspiration biopsy diagnosis of mucoepidermoid carcinoma, statistical analysis. Acta Cytol 1990;34:43-49 21. Wenig B, Adair CF, Heffess CS: Primary mucoepidermoid carcinoma of the thyroid gland: A report of six cases and a review of the literature of a follicular epithelial-derived tumor. Hum Pathol 1995;26:1099-1108 22. Goode RK, Auclair PL, Ellis GL: Mucoepidermoid carcinoma of the major salivary glands. Clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 1998;82:1217-1224