ARTICLE IN PRESS
YBJOM-4495; No. of Pages 3
Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Short communication
Keratocystoma of the parotid gland: a case report and review of previous publications Weiya Wang a , Yi Li b , Ying Tang a,∗ a b
Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China Department of Head & Neck Oncology, West China hospital of Stomatology, Sichuan University, Chengdu 610041, China
Accepted 4 April 2015
Abstract Keratocystoma is a rare benign tumour of the salivary glands. We report a patient who presented with a mass in the left parotid gland that was treated by subtotal parotidectomy and he was free of recurrence seven years later. After histological and immunohistochemical examinations we identified a keratocystoma. © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Keratocystoma; Benign tumour; Parotid gland; Differential diagnosis; Prognosis
Introduction Keratocystoma is a rare benign lesion of the salivary gland1 that is characterised by multicystic spaces lined with stratified squamous cells containing keratotic lamellae and focal solid epithelial nests, with no necrosis, invasion, or cytological atypia, and it does not metastasise.2 To our knowledge only six cases have been reported to date.3–6 Here we present a new case and review of previous publications (Table 1). Case report A 34-year-old man presented with hypothyroidism and a gradually enlarging, hard, and painful mass below the left auricular lobule for two months. The local skin looked normal, and he had no cervical lymphadenopathy. There was no history of either systemic or hereditary diseases, and we ∗
Corresponding author. Tel.: +86 28 85423765; fax: +86 28 85422698. E-mail addresses: wang [email protected] (W. Wang), [email protected] (Y. Li), [email protected] (Y. Tang).
suspected a Warthin tumour or inflammatory disease. The mass did not respond to a 2-week course of penicillin, so we did a subtotal parotidectomy. The mass was located in the lower lobe of the parotid gland with a complete capsule. There were many small cystic spaces, which contained a white chylous substance on the cut surface. Microscopically the lesion consisted of irregularlydistributed multiple cystic structures and solid nests of squamous cells. The cystic spaces were filled with keratotic lamellae with no regular shape (Fig. 1). The cysts and solid nests showed some bud-like or pin-like protrusions into the stroma (Fig. 2). The intercalated ducts, which were mostly clustered together, were close to the outer layers of the nests and their protruding buds (Fig. 2). The ductal cells showed a squamous metaplastic-like process with no remaining lumina, and gradually transformed into solid nests (Fig. 3). The nests and cysts were lined with benign squamous epithelium with orthokeratosis or parakeratosis, but had no granular layer. Squamous cells had bland nuclei and eosinophilic cytoplasm with no atypical morphology (Fig. 2), and there was no necrosis or granulomas in any
http://dx.doi.org/10.1016/j.bjoms.2015.04.005 0266-4356/© 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wang W, et al. Keratocystoma of the parotid gland: a case report and review of previous publications. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.04.005
YBJOM-4495; No. of Pages 3
2
ARTICLE IN PRESS W. Wang et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Table 1 Clinicopathological features of seven cases of keratocystoma. First author and reference no.
Sex/age (years)
Duration of symptoms
Side
Size of tumour (mm)
Foreign body reaction
Residual parotid gland
Time without recurrence
Seifert3
Female/8
1 month
Right
13 (diameter)
Yes
No details
Nagao4
Male/18
4 months
Right
40 × 30 × 15
Yes
Nagao4 Zhang5 Huang6
Male/38 Male/37 Female/29
12 months 6 years 2 years
Left Left Right
40 × 35 × 30 20 × 18 × 15 25 × 20 × 20
Yes No Yes
Huang6
Female/49
2 months
Right
25 × 20 × 15
Yes
Present case
Male/34
6 months
Left
30 × 30 × 25 mm
No
Near the cysts and nests Atrophic, fibrosis, and inflammation Atrophic Not mentioned Near the cysts and nests Near the cysts and nests Fibrosis and inflammation
Fig. 1. Irregularly-distributed multiple cystic structures and solid nests of squamous cells with obvious proliferation of fibrous tissue in the stroma (haematoxylin and eosin, original magnification × 40).
of the sections, but there were signs of fibrosis and chronic infiltration of inflammatory cells in the adjacent parenchyma of the parotid gland. Immunohistochemical examination showed that Ki-67stained cells were restricted to the basal layer of the cysts and nests. The tumour cells in the nests and the basal layers of the cystic formations stained strongly and weakly for p63 and p53, respectively. There were no signs of EpsteinBarr virus (EBV) or human papilloma virus (HPV) on in situ hybridisation. The patient remains well seven years later, and has no evidence of recurrent disease.
3 years 2 years 18 months 4 years 3 years 3 years
Fig. 2. Bud-like or pin-like protrusions into the stroma close to the proliferating intercalated ducts. The cyst wall is lined with benign stratified squamous epithelium and orthokeratosis or parakeratosis without a granular layer (haematoxylin and eosin, original magnification × 100).
Keratocystoma in the parotid gland can present from 8 to 49 years.3–6 These tumours expand slowly and have been accompanied by pain in three cases. A foreign-body reaction against keratin caused by rupture of the cysts was found in five
Discussion Nagao et al. reported two histologically identical cases in men and they designated the tumour “keratocystoma” for the first time.4 Keratocystoma was listed as a differential diagnosis of squamous cell carcinoma (SCC) of the salivary gland by the WHO working group in 2005.2
Fig. 3. The ducts around the nests show squamous metaplastic-like change, transformed into a solid nest (haematoxylin and eosin, original magnification × 100).
Please cite this article in press as: Wang W, et al. Keratocystoma of the parotid gland: a case report and review of previous publications. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.04.005
ARTICLE IN PRESS
YBJOM-4495; No. of Pages 3
W. Wang et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
cases. No patient was given additional treatment apart from subtotal parotidectomy, and none had evidence of recurrence or malignant transformation.3–6 The exact pathogenesis is unknown because of its rarity, but overexpression of p63 and p53 imply neoplastic proliferation. To exclude viral infection of the oropharynx, and metastases of nasopharyngeal carcinoma, we looked for EPV and HPV but in situ hybridisation showed this to be unlikely. Every case showed squamous metaplasia of the intercalated ducts and their gradual transformation into solid nests. The most important differential diagnosis was welldifferentiated SCC in which the facial nerve is often involved, and there are solid nests and cystic changes.7 The low index of Ki-67, the benign cytological morphology, and the clinical course of our patient confirm the benign nature of his keratocystoma. The lack of mucus cells and widespread keratinisation help to distinguish a keratocystoma from a mucoepidermoid carcimoma. The squamous odontogenic tumour or keratocystic odontogenic tumour may also be considered, in which multiple well-differentiated squamous nests and cysts can also be seen. In our patient the ducts gradually transformed into nests, which clearly ruled out a relation to the odontogenic tumours. In addition, the lack of a granular layer in the cysts of the keratocystoma has a major role in its differentiation from a benign lesion such as an epidermoid cyst or a trichoadenoma. In conclusion, pathologists and clinicians should be aware of this rare lesion to distinguish it from well-differentiated SCC. Local conservative excision is adequate treatment if the diagnosis is accurate.
3
Ethics statement/confirmation of patient’s permission Ethics approval was provided by the Institutional Review Board of the Hospital.
Funding This work was supported by grants from the National Natural Science Foundation of China (no. 81302027).
References 1. Cheuk W, Chan JK. Advances in salivary gland pathology. Histopathology 2007;51:1–20. 2. Lewis JE, Olsen KD. Squamous cell carcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. Pathology and genetics of head and neck tumours. WHO classification of tumours. Lyon: ARC Press; 2005. p. 245–6. 3. Seifert G, Donath K, Jautzke G. Unusual choristoma of the parotid gland in a girl. A possible trichoadenoma. Virchows Arch 1999;434: 355–9. 4. Nagao T, Serizawa H, Iwaya K, et al. Keratocystoma of the parotid gland: a report of two cases of an unusual pathologic entity. Mod Pathol 2002;15:1005–10. 5. Zhang MF, Lin SX, Yi C, et al. Keratocystoma of the parotid gland: case report and immunohistochemical investigation. J Clin Pathol 2010;63:758–60. 6. Huang XF, Li W, Yang XD, et al. Keratocystoma of the parotid gland: a clinicopathological study and literature review. Int J Oral Maxillofac Surg 2012;41:256–60. 7. Flynn MB, Maguire S, Martinez S, et al. Primary squamous cell carcinoma of the parotid gland: the importance of correct histological diagnosis. Ann Surg Oncol 1999;6:768–70.
Conflict of interest We have no conflict of interest.
Please cite this article in press as: Wang W, et al. Keratocystoma of the parotid gland: a case report and review of previous publications. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.04.005
YBJOM-4495; No. of Pages 3
Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Short communication
Keratocystoma of the parotid gland: a case report and review of previous publications Weiya Wang a , Yi Li b , Ying Tang a,∗ a b
Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China Department of Head & Neck Oncology, West China hospital of Stomatology, Sichuan University, Chengdu 610041, China
Accepted 4 April 2015
Abstract Keratocystoma is a rare benign tumour of the salivary glands. We report a patient who presented with a mass in the left parotid gland that was treated by subtotal parotidectomy and he was free of recurrence seven years later. After histological and immunohistochemical examinations we identified a keratocystoma. © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Keratocystoma; Benign tumour; Parotid gland; Differential diagnosis; Prognosis
Introduction Keratocystoma is a rare benign lesion of the salivary gland1 that is characterised by multicystic spaces lined with stratified squamous cells containing keratotic lamellae and focal solid epithelial nests, with no necrosis, invasion, or cytological atypia, and it does not metastasise.2 To our knowledge only six cases have been reported to date.3–6 Here we present a new case and review of previous publications (Table 1). Case report A 34-year-old man presented with hypothyroidism and a gradually enlarging, hard, and painful mass below the left auricular lobule for two months. The local skin looked normal, and he had no cervical lymphadenopathy. There was no history of either systemic or hereditary diseases, and we ∗
Corresponding author. Tel.: +86 28 85423765; fax: +86 28 85422698. E-mail addresses: wang [email protected] (W. Wang), [email protected] (Y. Li), [email protected] (Y. Tang).
suspected a Warthin tumour or inflammatory disease. The mass did not respond to a 2-week course of penicillin, so we did a subtotal parotidectomy. The mass was located in the lower lobe of the parotid gland with a complete capsule. There were many small cystic spaces, which contained a white chylous substance on the cut surface. Microscopically the lesion consisted of irregularlydistributed multiple cystic structures and solid nests of squamous cells. The cystic spaces were filled with keratotic lamellae with no regular shape (Fig. 1). The cysts and solid nests showed some bud-like or pin-like protrusions into the stroma (Fig. 2). The intercalated ducts, which were mostly clustered together, were close to the outer layers of the nests and their protruding buds (Fig. 2). The ductal cells showed a squamous metaplastic-like process with no remaining lumina, and gradually transformed into solid nests (Fig. 3). The nests and cysts were lined with benign squamous epithelium with orthokeratosis or parakeratosis, but had no granular layer. Squamous cells had bland nuclei and eosinophilic cytoplasm with no atypical morphology (Fig. 2), and there was no necrosis or granulomas in any
http://dx.doi.org/10.1016/j.bjoms.2015.04.005 0266-4356/© 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wang W, et al. Keratocystoma of the parotid gland: a case report and review of previous publications. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.04.005
YBJOM-4495; No. of Pages 3
2
ARTICLE IN PRESS W. Wang et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Table 1 Clinicopathological features of seven cases of keratocystoma. First author and reference no.
Sex/age (years)
Duration of symptoms
Side
Size of tumour (mm)
Foreign body reaction
Residual parotid gland
Time without recurrence
Seifert3
Female/8
1 month
Right
13 (diameter)
Yes
No details
Nagao4
Male/18
4 months
Right
40 × 30 × 15
Yes
Nagao4 Zhang5 Huang6
Male/38 Male/37 Female/29
12 months 6 years 2 years
Left Left Right
40 × 35 × 30 20 × 18 × 15 25 × 20 × 20
Yes No Yes
Huang6
Female/49
2 months
Right
25 × 20 × 15
Yes
Present case
Male/34
6 months
Left
30 × 30 × 25 mm
No
Near the cysts and nests Atrophic, fibrosis, and inflammation Atrophic Not mentioned Near the cysts and nests Near the cysts and nests Fibrosis and inflammation
Fig. 1. Irregularly-distributed multiple cystic structures and solid nests of squamous cells with obvious proliferation of fibrous tissue in the stroma (haematoxylin and eosin, original magnification × 40).
of the sections, but there were signs of fibrosis and chronic infiltration of inflammatory cells in the adjacent parenchyma of the parotid gland. Immunohistochemical examination showed that Ki-67stained cells were restricted to the basal layer of the cysts and nests. The tumour cells in the nests and the basal layers of the cystic formations stained strongly and weakly for p63 and p53, respectively. There were no signs of EpsteinBarr virus (EBV) or human papilloma virus (HPV) on in situ hybridisation. The patient remains well seven years later, and has no evidence of recurrent disease.
3 years 2 years 18 months 4 years 3 years 3 years
Fig. 2. Bud-like or pin-like protrusions into the stroma close to the proliferating intercalated ducts. The cyst wall is lined with benign stratified squamous epithelium and orthokeratosis or parakeratosis without a granular layer (haematoxylin and eosin, original magnification × 100).
Keratocystoma in the parotid gland can present from 8 to 49 years.3–6 These tumours expand slowly and have been accompanied by pain in three cases. A foreign-body reaction against keratin caused by rupture of the cysts was found in five
Discussion Nagao et al. reported two histologically identical cases in men and they designated the tumour “keratocystoma” for the first time.4 Keratocystoma was listed as a differential diagnosis of squamous cell carcinoma (SCC) of the salivary gland by the WHO working group in 2005.2
Fig. 3. The ducts around the nests show squamous metaplastic-like change, transformed into a solid nest (haematoxylin and eosin, original magnification × 100).
Please cite this article in press as: Wang W, et al. Keratocystoma of the parotid gland: a case report and review of previous publications. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.04.005
ARTICLE IN PRESS
YBJOM-4495; No. of Pages 3
W. Wang et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
cases. No patient was given additional treatment apart from subtotal parotidectomy, and none had evidence of recurrence or malignant transformation.3–6 The exact pathogenesis is unknown because of its rarity, but overexpression of p63 and p53 imply neoplastic proliferation. To exclude viral infection of the oropharynx, and metastases of nasopharyngeal carcinoma, we looked for EPV and HPV but in situ hybridisation showed this to be unlikely. Every case showed squamous metaplasia of the intercalated ducts and their gradual transformation into solid nests. The most important differential diagnosis was welldifferentiated SCC in which the facial nerve is often involved, and there are solid nests and cystic changes.7 The low index of Ki-67, the benign cytological morphology, and the clinical course of our patient confirm the benign nature of his keratocystoma. The lack of mucus cells and widespread keratinisation help to distinguish a keratocystoma from a mucoepidermoid carcimoma. The squamous odontogenic tumour or keratocystic odontogenic tumour may also be considered, in which multiple well-differentiated squamous nests and cysts can also be seen. In our patient the ducts gradually transformed into nests, which clearly ruled out a relation to the odontogenic tumours. In addition, the lack of a granular layer in the cysts of the keratocystoma has a major role in its differentiation from a benign lesion such as an epidermoid cyst or a trichoadenoma. In conclusion, pathologists and clinicians should be aware of this rare lesion to distinguish it from well-differentiated SCC. Local conservative excision is adequate treatment if the diagnosis is accurate.
3
Ethics statement/confirmation of patient’s permission Ethics approval was provided by the Institutional Review Board of the Hospital.
Funding This work was supported by grants from the National Natural Science Foundation of China (no. 81302027).
References 1. Cheuk W, Chan JK. Advances in salivary gland pathology. Histopathology 2007;51:1–20. 2. Lewis JE, Olsen KD. Squamous cell carcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. Pathology and genetics of head and neck tumours. WHO classification of tumours. Lyon: ARC Press; 2005. p. 245–6. 3. Seifert G, Donath K, Jautzke G. Unusual choristoma of the parotid gland in a girl. A possible trichoadenoma. Virchows Arch 1999;434: 355–9. 4. Nagao T, Serizawa H, Iwaya K, et al. Keratocystoma of the parotid gland: a report of two cases of an unusual pathologic entity. Mod Pathol 2002;15:1005–10. 5. Zhang MF, Lin SX, Yi C, et al. Keratocystoma of the parotid gland: case report and immunohistochemical investigation. J Clin Pathol 2010;63:758–60. 6. Huang XF, Li W, Yang XD, et al. Keratocystoma of the parotid gland: a clinicopathological study and literature review. Int J Oral Maxillofac Surg 2012;41:256–60. 7. Flynn MB, Maguire S, Martinez S, et al. Primary squamous cell carcinoma of the parotid gland: the importance of correct histological diagnosis. Ann Surg Oncol 1999;6:768–70.
Conflict of interest We have no conflict of interest.
Please cite this article in press as: Wang W, et al. Keratocystoma of the parotid gland: a case report and review of previous publications. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.04.005
