Accepted Manuscript Primary Intraosseous Squamous Cell Carcinoma Arising From Keratocystic Odontogenic Tumour Ochiba Mohammed Lukandu, BDS, PhD, Dr., Cyrus Songwa Micha, BDS, MDS, Dr. PII:

S2212-4403(15)00584-2

DOI:

10.1016/j.oooo.2015.03.006

Reference:

OOOO 1167

To appear in:

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Received Date: 13 November 2014 Revised Date:

10 February 2015

Accepted Date: 16 March 2015

Please cite this article as: Mohammed Lukandu O, Songwa Micha C, Primary Intraosseous Squamous Cell Carcinoma Arising From Keratocystic Odontogenic Tumour, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2015), doi: 10.1016/j.oooo.2015.03.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Page 1 of 19

Primary Intraosseous Squamous Cell Carcinoma Arising From Keratocystic Odontogenic Tumour Authors

RI PT

Dr. Ochiba Mohammed Lukandua BDS, PhD, Lecturer and Oral Pathologist [email protected] and

[email protected] a

SC

Dr. Cyrus Songwa Michaa BDS, MDS, Lecturer and Oral and Maxillofacial Surgeon

Department of Oral and Maxillofacial Surgery, Oral Medicine, Pathology and Radiology,

Corresponding author;

M AN U

School of Dentistry, Moi University, Eldoret, Kenya.

Dr. Ochiba Mohammed Lukandu BDS, PhD. School of Dentistry, Moi University P.O Box 4606-30100 Eldoret, Kenya

TE D

Email: [email protected]

Tel: +254774093004 (cell phone), Work place phone +254532030965 Work place Fax: +254532030966

EP

This work has not been submitted anywhere else for the purpose of publication. An abstract and an oral presentation of this case were made at the 32nd Kenya Dental Association conference on

AC C

30th October 2014 at Nairobi Kenya. We declare that we have no competing interests and that there was no specific funding for this work besides routine diagnostic and treatment procedures at the hospital. Abstract word count Complete word count of manuscript Number of references Number of tables Number of figures

= 142 = 4640 = 33 =2 =4

ACCEPTED MANUSCRIPT Page 2 of 19

ABSTRACT

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare lesion that almost exclusively

RI PT

occurs in the jaws. Most PIOSCC originate from epithelial lining of odontogenic cysts, especially from radicular, residual and dentigerous cysts. A few cases have been shown to arise from keratocystic odontogenic tumours (KCOT). This is a report of a case of PIOSCC that arose

SC

from an untreated keratocystic odontogenic tumour within a period of less than two years of first diagnosis. Upon malignant transformation, the tumour changed from a cystic to a solid pattern

M AN U

and acquired an infiltrative growth pattern invading and destroying all surrounding bone. This case underscores the importance of early diagnosis and treatment of KCOT and raises a question whether some of the PIOSCC classified as ‘solid type’ could in fact be late presenting PIOSCC

TE D

arising from KCOT and other cystic pathological entities within the jaws.

Keywords:, primary intra-osseous squamous cell carcinoma, keratocystic odontogenic tumour,

AC C

EP

odontogenic, mandible.

ACCEPTED MANUSCRIPT Page 3 of 19

INTRODUCTION Primary intraosseous squamous cell carcinoma (PIOSCC) is a carcinoma arising within bone without any initial connection to the various epithelia in the body. It is a very rare condition that

RI PT

occurs almost exclusively in the jaws where it develops from intraosseous remnants of

odontogenic epithelium. For a diagnosis of PIOSCC, specific criteria to be met include absence of oral ulceration or communication with the overlying mucosa, absence of a distant primary

SC

tumour at the time of diagnosis and histological evidence of squamous cell carcinoma 1. Most intraosseous carcinomas originate from epithelial lining of odontogenic cysts, especially from

M AN U

radicular, residual and dentigerous cysts. They have therefore been termed odontogenic carcinomas. PIOSCC arising from keratocystic odontogenic tumour (KCOT) is very rare, comprising only about 16 cases out of all cases reported so far 2.

TE D

PURPOSE

The purpose of this paper is to report a unique case of a 34 year old female patient diagnosed with KCOT in August 2012 who only turned up for treatment when her condition worsened in

EP

March 2014. Histopathological assessment of the resected specimen showed that at the time of

AC C

treatment, the tumour had transformed to PIOSCC.

ACCEPTED MANUSCRIPT Page 4 of 19

CASE REPORT Case presentation in August 2012 A 32 year old female patient presented at the dental department at Moi Teaching and Referral

RI PT

Hospital, Eldoret, Kenya with mandibular swelling on the right side. She reported that the lesion started in 2009 as a small swelling in the vestibule next to the right posterior teeth. Even though the lesion was asymptomatic, she sought treatment at a local hospital where an x-ray

SC

(orthopantomograph or OPG) was taken which revealed a multilocular radiolucency in the right body of the mandible. The patient was referred for specialized treatment, but did not do so until

M AN U

three years later when the lesion had expanded to cause an obvious swelling. By then, the facial asymmetry was obvious but the lesion was still asymptomatic except for mild pain on chewing on the affected side. Clinical examination revealed a bony hard swelling on the right body of the mandible, but overlying skin and mucosa were normal in color, texture and consistency. There

TE D

were no palpable lymph nodes. A repeat OPG was done which showed a multilocular radiolucent lesion on the right side of the mandible extending from the premolar area to the angle of the

EP

mandible.

During an intraoral incisional biopsy procedure, the lesion appeared cystic in nature with whitish

AC C

jelly fluid within it. Microscopic examination of the tissue revealed empty spaces lined by stratified squamous odontogenic epithelium with palisaded basal cells, uniform in thickness, highly folded and friable (Figure 1). The surface of the epithelium was corrugated and showed parakeratinization and orthokeratinization in some areas. Features suggestive of dysplasia such as nuclear hyperchromatism and pleomorphism were noted in a few areas within the epithelium. The connective tissue was loose and fibrous and reactive bone deposition mainly in form of thin

ACCEPTED MANUSCRIPT Page 5 of 19

trabeculae of woven bone and osteoid were noted. A histological diagnosis of keratocystic odontogenic tumour was made. A treatment protocol of segmental resection of the mandible and reconstruction with a titanium plate was discussed with the patient. However, the patient did not

RI PT

turn up for treatment until the year 2014 when the lesion became symptomatic.

Case presentation in March 2014

SC

About two years later, the patient presented with a much larger swelling with associated pain, and there was a scar suggestive of a healed discharging sinus on the right cheek (Figure 2A).

M AN U

There were two palpable ipsilateral lymph nodes. A repeat OPG was done which revealed an extensive loss of mandibular bone involving the right body, ramus and coronoid process and extending to the condylar process as well (Figure 2B). On the basis of the previous histological diagnosis done in 2012, a right hemimandibulectomy with disarticulation of the affected TMJ

TE D

was done. The specimen was sent for histopathological assessment. A week later, mandibular reconstruction with a Titanium angled plate without TMJ prosthesis was done. The patient responded well to this treatment and is still undergoing scheduled follow up sessions at the

EP

hospital.

AC C

Laboratory handling of gross specimen in March 2014 Specimens received in the laboratory were of the right hemimandibulectomy from the lower right canine with disarticulation and two lymph nodes all fixed in adequate amounts of formalin. The hemimandible had a mass extending from the region of lower right first molar all the way to the condylar and coronoid processes. The mass was firm, but did not have any bony hard areas and appeared to be enclosed within fibrous remnants of the periostium. The mass was first

ACCEPTED MANUSCRIPT Page 6 of 19

sectioned sagitally and coronally in the middle into four pieces. This revealed the inner part which consisted of whitish solid tissue that was uniformly firm. The lesion had completely destroyed and replaced all bone, as no bony elements were noted within or around it including at

RI PT

the coronoid and condylar processes. Fibrous remnants of the periostium were noted enclosing some parts of the lesion, and were continuous with the fibrous insertion of the temporalis muscle at the coronoid process. Further serial sections were made for the entire lesion and pieces of

SC

tissue were taken from various sites for histological preparation and microscopy. The lymph nodes were also firm and one measured 2 cm while the other measured 3 cm in length and both

Histological appearance in March 2014

M AN U

were about 1 cm in width. Both were serially sectioned for histological examination.

Most of the tumour, particularly the central sections, presented a uniform pattern of dense highly

TE D

folded stratified squamous epithelium that was nonkeratinized in most areas and parakeratinized in a few areas. The intense folding of the epithelium obliterated cystic spaces leaving only small clefts in a few areas which contained varying amounts of keratin and degenerating cells (Figure

EP

3A). The basement membrane seemed intact in these areas but the lesion seemed to push and fold into the connective tissue stroma and to merge forming large solid epithelial islands (Figure

AC C

3B). A few areas showed dysplastic changes within the hyperplastic epithelium in form of cellular and nuclear pleomorphism, hyperchromatism and dyskeratosis.

In other sections of the tumour, especially around tumour margins, it presented invasive fronts composed of single cells or small sheets of cells and islands of neoplastic squamous epithelium with marked nuclear pleomorphism, hyperchromatism, atypia and bizarre mitotic figures.

ACCEPTED MANUSCRIPT Page 7 of 19

Individual cell keratinization was also evident, but well formed keratin pearls were absent (Figure 4). Tumour invasion into adjacent connective tissue was noted, particularly infiltration into the fibrous remnants of the periostium at the margins of the tumour. The connective tissue

RI PT

showed infiltration by mainly chronic inflammatory cells which consisted of lymphocytes and plasma cells. In some sections, there were mixed inflammatory cells suggestive of bacterial

infection within the tumour. Both lymph nodes were reactive with well formed germinal centres,

SC

but there was no evidence of tumour cells within them. A histological diagnosis of infiltrative

M AN U

squamous cell carcinoma was made.

DISCUSSION

Epithelial remnants of odontogenic embryonic tissues are a normal finding in the jaws and some of these cells do give rise to various pathological entities such as cysts and tumors. Squamous

TE D

cell carcinomas arising in jawbones were first described about 100 years ago 3 and there have been several revisions in their nomenclature ever since 4. The term ‘primary intra-osseous

EP

squamous cell carcinoma’ (PIOSCC) was first used by Eversole et al 5, who then classified these tumours into three sub-types namely 1) solid type tumours, 2) carcinomas arising from

AC C

odontogenic cysts and 3) carcinomas associated with odontogenic tumours. Classification of PIOSCC has evolved over time as new information emerges about their origin and biological behavior (Tables 1and 2). In the most recent WHO Classification of Tumors of 2005, PIOSCC is classified into three subcategories: 1) solid type carcinoma, 2) PIOSCC arising from odontogenic cysts and 3) PIOSCC arising from keratocystic odontogenic tumors 6, 7, (Table 2).

ACCEPTED MANUSCRIPT Page 8 of 19

PIOSCC are very rare conditions, with less than 150 cases having been reported in the literature since 1938 8. They are thought to account for less than 2% of all oral cancer cases 2 and also less than 2% of all odontogenic tumours 9. They occur most often in the elderly with a mean age of

RI PT

60 years. Over 80% of these lesions occur between the fifth and seventh decades 4, 8. The

conditions have a slight male predilection 10, 11 with an estimated male: female ratio of 3:1. 12. PIOSCC affects the mandible more often (79%) than the maxilla (21%) 13-16 and is especially

SC

common at the body and ramus of mandible. Various odontogenic cysts have been associated with PIOSCC, including residual cyst, dentigerous cyst, calcifying odontogenic cyst, and lateral

M AN U

periodontal cyst. Cysts most commonly associated with PIOSCC are inflammatory residual cysts accounting for about 38% followed by dentigerous cysts accounting for about 19% of all PIOSCC 3, 17, 18.

TE D

KCOT is defined as a benign unicystic or multicystic intraosseous tumor of odontogenic origin with a characteristic lining of parakeratinized stratified squamous epithelium, with potential for aggressive and infiltrative behavior 19. KCOT was previously classified as a cyst known as

EP

odontogenic keratocyst which was noted to have an aggressive biological potential 20. Suggestions to have it reclassified into a tumour were made as early as 1967 19, but it was not

AC C

until genetic evidence for this became available that it was reclassified in 2003. Despite the aggressive nature of KCOT, cases of PIOSCC arising from it are few. Only 7 cases of malignant transformation of KCOT had been reported in the literature by 1996 21. This number rose to 12 cases in 2002 22 and to about 16 cases by 2013 2, 8, 17.

ACCEPTED MANUSCRIPT Page 9 of 19

The case we report here fits the diagnostic criteria for PIOSCC according to various previous publications 4, 23, 24 because there was no clinical evidence of a carcinoma in any other part of the patient’s body, there was microscopic confirmation of squamous cell carcinoma and the

RI PT

overlying oral mucosa and skin were intact. Furthermore, the case fits the type of PIOSCC that arises from KCOT in two ways. First, there was evidence of a longstanding KCOT in the same part of the body which had histological evidence of dysplasia at the time of initial diagnosis.

SC

Secondly, in addition to the bulk of the tumor depicting invasive carcinoma, a few sections

suggested a previous KCOT.

M AN U

showed highly folded but uniform odontogenic epithelium and remnants of cytic spaces that

With regard to the pathogenesis of PIOSCC, one suggested hypothesis is the role of chronic inflammation 25 and effect of the ensuing immunosuppression as well as reactive oxygen species

TE D

on remnants of dental lamina and odontogenic cysts. Longstanding chronic inflammation has been suggested as a key predisposing factor for malignant transformation of odontogenic cysts and benign odontogenic tumours. 26. Evidence of chronic infection in the period prior to PIOSCC

EP

has been reported in previous cases 3. In this case, the long duration without treatment might have predisposed the lesion to infective processes, especially during biopsy procedures. Indeed,

AC C

the patient presented with clinical evidence of chronic infection within the lesion, and there was histological evidence of infiltration by mixed inflammatory cells such lymphocytes, plasma cells and neutrophils in the connective tissue stroma around and within the lesion.

Clinically, this case presented with symptoms such as pain and swelling, which is in agreement with those reported in most of the previous cases 27. Absence of paraesthesia in this case is

ACCEPTED MANUSCRIPT Page 10 of 19

similar to what has been reported in a few reports 13 and could suggest a recent malignant transformation. PIOSCC generally occurs in older patients 4, 8, but a look at the few PIOSCC arising from KCOT suggests that these tend to occur in younger patients than those arising from

RI PT

odontogenic cysts 14, 21. Transformation of a benign cyst to a carcinoma could occur in a period of 10 years 28 with overall transformation rates of about 0.13 to 2% for odontogenic cysts.

Transformation rates for KCOT are not known, but in this case, transformation occurred in less

SC

than five years of the appearance of the first signs and symptoms.

M AN U

Histologically, most cases of PIOSCC present as well differentiated or moderately differentiated squamous cell carcinoma, and could be keratinizing or nonkeratinizing 12. It has previously been suggested 29 that the histological criteria for PIOSCC diagnosis should include confirmation of a transitional area between the usual epithelium of the cyst and the infiltrative squamous cell

TE D

carcinoma. In this case, the histological features shown in figure 3 are clearly a transition between those shown in figure 1 and those shown in figure 4. However, in cases where the PIOSCC is aggressive and destructive, the carcinoma could destroy and replace all normal and

AC C

determine.

EP

pathological entities preceding it, and a transitional area of any kind might be difficult to

Panda et al have suggested that the histological appearance of PIOSCC arising from KCOT is typically that of a keratinizing well differentiated squamous cell carcinoma 6. Loss of keratinization as KCOT transforms to PIOSCC has been noted in a previous report 21. In this case, we note an obvious decrease in keratinization after the KCOT transformed to PIOSCC, with fully transformed and infiltrative sections of the tumour depicting a pattern of

ACCEPTED MANUSCRIPT Page 11 of 19

undifferentiated squamous cell carcinoma. It is therefore possible that some PIOSCC arising from KCOT could present as undifferentiated squamous cell carcinoma.

RI PT

Radiographically, KCOT often present as a multilocular lesion and does not present with buccolingual cortical bone expansion. Radiographic appearance of PIOSCC can vary but often present as multilocular lesions with ill or well defined margins 30. Solid type PIOSCC is thought to

SC

display osteolytic appearance with ill defined irregular margins, whereas the other types display well defined margins especially during the early stages 10. In this case, the lesion was initially a

M AN U

multilocular radiolucency with well defined margins on panoramic radiographs in 2012. However, in 2014, all surrounding bone was destroyed and the anterior margin appeared to be ill defined, resembling radiological appearance in osteomyelitis. In general, malignant transformation to PIOSCC in odontogenic cysts should be considered when radiological margins

TE D

appear diffuse, irregular with jagged indentations and indistinct borders 18, 30.

With regard to diagnosis of PIOSCC, Yamada et al proposed that serial sections of the

EP

histological specimens must demonstrate squamous cell carcinoma without cystic components in order to rule out the possibility of other odontogenic carcinomas 3. As demonstrated in this case,

AC C

the gross and histological appearance could change drastically within a very short time as the benign lesion transforms to a carcinoma. At the time of diagnosis of PIOSCC, there could be no evidence left of a previous cystic entity or tumour.

Of further interest, this tumour did not show obvious cystic spaces both at gross and at microscopic examination at the time of treatment in the year 2014 as it did at the time of first

ACCEPTED MANUSCRIPT Page 12 of 19

diagnosis in the year 2012. In the absence of all information of 2012, and the numerous serial sections of histological specimens done to reveal remnants of cystic spaces and odontogenic epithelium as shown in figure 3A, this tumour could probably have been classified as solid type

RI PT

PIOSCC according to the latest WHO classification of head and neck tunours 7. A question then arises whether some of the PIOSCC classified as solid type PIOSCC could in fact be late

SC

presentations of PIOSCC arising from KCOT and other cystic pathological entities in the jaws.

It has been noted that PIOSCC generally has a poor prognosis, with 5-year survival as low 30 to

M AN U

40% 3, 31. However, PIOSCC that arise from odontogenic cysts has somewhat better prognosis when compared to those classified as solid type 3, 18. This observation could support the view that some carcinomas classified as solid type PIOSCC could in fact be late presenting carcinomas of varying origin, hence the much lower survival rates. As has been suggested before, 1, 32, this is

TE D

an area that needs further research to inform future diagnostic criteria and classification. Lymph node metastasis occurs in about 50% of the PIOSCC arising from KCOT 17, and management usually involves wide radical surgical resection and neck dissection with or without radiotherapy

EP

and chemotherapy 17, 26. Local recurrence has been reported to occur in about 20% of cases, and

AC C

regional and distant metastases in almost 30% 17.

CONCLUSION

This case report highlights the importance of early diagnosis and management of benign odontogenic tumours and the potential risk of malignant transformation in cases where treatment is delayed. Furthermore, it raises the question whether some of the PIOSCC classified as ‘solid type’ could in fact be late presentations of PIOSCC arising from KCOT and other cystic pathological conditions of the jaws.

ACCEPTED MANUSCRIPT Page 13 of 19

CONFLICT OF INTEREST

RI PT

We declare that we have no competing interests.

ETHICS

All information provided for publication was discussed and agreed upon with the patient and she

SC

signed a written consent form allowing the publication. The hospital authorities also provided a

ACKNOWLEDGEMENTS

M AN U

written permission for this publication.

The authors would like to thank the patient and management of Moi Teaching and referral Hospital for permission to publish this work and the laboratory staff at the hospital who assisted

REFERENCES

TE D

in preparation of histological sections.

EP

1) Pardhe, N., Bhagalia, S., Nayak, P. A., and Sireesha, S. K. Primary intraosseous

AC C

squamous cell carcinoma: a devil in disguise. BMJ Case Rep. 2013; 2013 2) Tan,V., Yan, T. S., Shermin, L., Teck, K. C.,Yoke, P. C., Goh, C., and Balakrishnan, A. Malignant transformation of keratocystic odontogenic tumor: two case reports. Am J Otolaryngol. 2013; 34: 357-361

3) Yamada, T., Ueno, T., Moritani, N., Mishima, K., Hirata, A., and Matsumura, T. Primary intraosseous squamous cell carcinomas: five new clinicopathologic case studies. J Craniomaxillofac Surg. 2009; 37: 448–453

ACCEPTED MANUSCRIPT Page 14 of 19

4) Thomas, G., Pandey, M., Mathew, A., Abraham, E.K., Francis, A., Somanathan, T. et al. Primary intraosseous carcinoma of the jaw: pooled analysis of world literature and report of two new cases. Int J Oral Maxillofac Surg. 2001; 30: 349–355

RI PT

5) Eversole, L.R., and Van der Waal I., Primary intraosseous squamous cell carcinomas, E. J. Barnes L, Reichart P, Sidransky D, Eds., Pathology and genetics of head and neck tumors, IACR Press, Lyon, 2005

SC

6) Panda, S., Sahoo, S. R., Srivastav, G., Padhiary, S., Dhull, K. S. and Aggarwal, S.

2014

M AN U

Pathogenesis and nomenclature of odontogenic carcinomas: revisited. J Oncol. 2014;

7) Barnes, L., Eveson, J.W., Reichart, P., Sidransky, D., and International Agency for Research on Cancer. Pathology and genetics of head and neck tumours. in: IARC, Lyon; 2005: 290–291

TE D

8) Bodner, L., Manor, E., Shear, M., and van der Waal, I. Primary intraosseous squamous cell carcinoma arising in an odontogenic cyst: a clinicopathologic analysis of 116 reported cases. J Oral Pathol Med. 2011; 40: 733–738

EP

9) Zapala-Pospiech, A., Wyszynska-Pawelec, G., Adamek, D., Tomaszewska, R., Zaleska, M., and Zapala, J. Malignant transformation in the course of a dentigerous cyst: a

AC C

problem for clinician and a pathologist. Considerations based on a case report. Pol J Pathol. 2013; 64: 64-68

10) Matsuzaki, H., Katase, N., Matsumura, T., Hara, M., Yanagi, Y., Nagatsuka, H., Iida, S., and Asaumi, J. Solid-type primary intraosseous squamous cell carcinoma of the mandible: a case report with histopathological and imaging features. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 114: 71-77

ACCEPTED MANUSCRIPT Page 15 of 19

11) Lugakingira, M., Pytynia, K., Kolokythas, A., and Miloro, M. Primary intraosseous carcinoma of the mandible: case report and review of the literature. J Oral Maxillofac Surg. 2010; 6: 2623-2629

RI PT

12) Elzay, R.P. Primary intraosseous carcinoma of the jaws (Review and update of

odontogenic carcinomas) . Oral Surg Oral Med Oral Pathol. 1982; 54: 299–303

13) Tamgadge, S., Tamgadge, A., Modak, N., and Bhalerao, S. Primary intraosseous

SC

squamous cell carcinoma arising from an odontogenic keratocyst: a case report and literature review. Ecancermedicalscience . 2013; 7:316

M AN U

14) Falaki, F., Delavarian, Z., Salehinejad, J., and Saghafi, S. Squamous cell carcinoma arising from an odontogenic keratocyst: a case report. Med Ora, Patol Oral Cir Bucal. 2009; 14:171-174

15) Scheer, M., Koch, A.M., Drebber, U., and Kübler, A.C. Primary intraosseous

TE D

carcinoma of the jaws arising from an odontogenic cyst—a case report. J Craniomaxillofac Surg. 2004; 32: 166–169 16) Swinson, B. D., Jerjes, W., and Thomas, G. J. Squamous cell carcinoma arising in a

EP

residual odontogenic cyst: case report. J Oral Maxillofac Surg. 2005; 63:1231-1233 17) Woolgar, J.A., Triantafyllou, A., Ferlito, A., Devaney, K.O., Lewis, J.S. Jr, Rinaldo, A. et

AC C

al. Intraosseous carcinoma of the jaws: a clinicopathologic review (Part III: primary

intraosseous squamous cell carcinoma). Head Neck. January 31 2012; (Epub ahead of print)

18) Chaisuparat, R., Coletti, D., Kolokythas, A., Ord, R.A., and Nikitakis, N.G. Primary intraosseous odontogenic carcinoma arising in an odontogenic cyst or de novo: a

ACCEPTED MANUSCRIPT Page 16 of 19

clinicopathologic study of six new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 101: 194–200

in the name? J Nat Sci Biol Med. 2013; 4: 282-285

RI PT

19) Nayak, M. T., Singh, A., Singhvi, A. and Sharma, R. Odontogenic keratocyst: What is

20) Eversole, L. R., Sabes, W. R., and Rovin, S. Aggressive growth and neoplastic

potential of odontogenic cysts: with special reference to central epidermoid and

SC

mucoepidermoid carcinomas. Cancer. 1975; 35: 270-282

21) Yoshida, H., Onizawa, K., and Yusa, H. Squamous cell carcinoma arising in

M AN U

association with an orthokeratinized odontogenic keratocyst. Report of a case. J Oral Maxillofac Surg. 1996; 54: 647-651

22) Keszler, A. and Piloni, M. J. Malignant transformation in odontogenic keratocysts. Case report. Med Oral. 2002; 331-335

TE D

23) Choi, Y. J., Oh, S. H., Kang, J. H., Choi, H. Y., Kim, G. T., Yu, J. J., Choi, Y. S., and Hwang, E. H. Primary intraosseous squamous cell carcinoma mimicking periapical disease: a case report. Imaging Sci Dent. 2012; 42: 265-270

EP

24) Sengupta, S., Vij, H., and Vij, R. Primary intraosseous carcinoma of the mandible: A report of two cases. J Oral Maxillofac Pathol. 2010; 14: 69–72

AC C

25) Browne R. M., and Gough, N. G. Malignant change in the epithelium lining odontogenic cysts. Cancer. 1972; 29: 1199-1207

26) Jain, M., Mittal, S., and Gupta, D. K. Primary intraosseous squamous cell carcinoma arising in odontogenic cysts: an insight in pathogenesis. J Oral Maxillofac Pathol. 2013; 71: 7-14

ACCEPTED MANUSCRIPT Page 17 of 19

27) MacLeod, R. I. and Soames, J. V. Squamous cell carcinoma arising in an odontogenic Keratocyst. J Oral Maxillofac Surg. 1988; 26:52-57 28) Araujo, J. P., Kowalski, L. P., Rodrigues, M. L., Almeida, O. P., Lopes Pinto, C. A. and

RI PT

Alves, F. A. Malignant transformation of an odontogenic cyst in a period of 10 years. Case Rep Dent. 2014; 2014

Carcinoma. Dent J. 1975; 41: 161-167

SC

29) Gardner, A. F., A survey of odontogenic cysts and their relationship to squamous cell

30) Cavalcanti, M.G., Veltrini, V.C., Ruprecht, A., Vincent, S.D., and Robinson, R.A.

M AN U

Squamous-cell carcinoma arising from an odontogenic cyst—the importance of computed tomography in the diagnosis of malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005; 100: 365–368

31) Tiwari, M. Primary intraosseous carcinoma of the mandible: A case report with

TE D

literature review. J Oral Maxillofac Pathol. 2011; 15: 205-210 32) Philipsen, H. P., and Reichart, P. A. Classification of odontogenic tumours. A historical review. J Oral Pathol Med. 2006; 35: 525-529

EP

33) Waldron, C.A. and Mustoe, T.A. Primary intraosseous carcinoma of the mandible with probable origin in an odontogenic cyst. Oral Surg Oral Med Oral Pathol. 1989;

AC C

67: 716–724

ACCEPTED MANUSCRIPT Page 18 of 19

FIGURE LEGENDS Figure 1. Histopathological presentation of the lesion in the year 2012. (Original magnification x200). Lesion showed empty spaces lined by stratified squamous odontogenic epithelium with

RI PT

palisaded basal cells, uniform in thickness, highly folded and friable. The surface of the

epithelium was corrugated and showed parakeratinization and orthokeratinization in some areas. Inset: A X400 magnification of the area marked X showing hyperchromatism and pleomorphism

SC

in suprabasal areas of the epithelium suggestive of moderate dysplasia. A high-resolution version

M AN U

of this slide for use with the Virtual Microscope is available as eSlide: VM00511 Figure 2. Presentation of the patient in the year 2014. A) A clinical photograph of the patient in 2014 showing obvious facial asymmetry with a large swelling over the right body, angle and ramus of the mandible (black arrow shows associated longstanding discharging sinus). B) Orthopantomograph of the patient in 2014 showing extensive loss of bone in the right body,

TE D

angle and ramus of the mandible.

Figure 3. Histopathological presentation of the lesion in the year 2014. (Original magnification

EP

x200). A) The lesion showed highly folded stratified squamous odontogenic epithelium with palisaded basal cells, uniform in thickness, largely nonkeratinizing, but with evidence of keratin

AC C

(K) in a few areas. Remnants of cystic spaces (S) are seen with debris that includes degenerating cells. In most areas, the basement membrane is intact, but the lesion pushes and folds into the connective tissue stroma as well. A high-resolution version of this slide for use with the Virtual Microscope is available as eSlide: VM00492. Panel B shows areas where the tumour is solid as epithelial folds merge to form large interconnected islands of neoplastic epithelium with occasional keratin (K) formation. There is minimal connective tissue stroma that shows mainly

ACCEPTED MANUSCRIPT Page 19 of 19

chronic inflammatory cell (F) infiltration. ‘A high-resolution version of this slide for use with the

RI PT

Virtual Microscope is available as eSlide: VM00510.’

Figure 4. Histopathological presentation of the lesion in the year 2014 (Original magnification x400). A) Tumour infiltration into adjacent fibrous connective tissue (C) is noted in form of sheets and islands of neoplastic epithelium. A high-resolution version of this slide for use with

SC

the Virtual Microscope is available as eSlide: VM00493. B) In other areas, especially near the

M AN U

tumour margins, the lesion presented tumour fronts depicting infiltration of connective tissue by streams and single cells of neoplastic squamous epithelium with marked nuclear pleomorphism, hyperchromatism, atypia and bizarre mitotic figures. In both cases, the connective tissue showed infiltration of mainly chronic inflammatory cells (F) which consisted of lymphocytes and plasma

AC C

EP

eSlide: VM00509.

TE D

cells. A high-resolution version of this slide for use with the Virtual Microscope is available as

ACCEPTED MANUSCRIPT

Type 2A

Metastasizing (malignant) ameloblastoma

Type 2B

Ameloblastic carcinoma

Type 3A

de novo PIOSCC, keratinizing type

Type 3B

de novo PIOSCC, nonkeratinizing type

Type 4

Intraosseous mucoepidermoid carcinoma

SC

PIOSCC arising from cysts

AC C

EP

TE D

M AN U

Type 1

RI PT

Table 1: Wadron and Mustoe's classification of PIOSCC 33

ACCEPTED MANUSCRIPT

Table 2: WHO 2005 classification of odontogenic carcinomas 6

RI PT

Malignant ameloblastoma Ameloblastic carcinoma - Primary type

Ameloblastic carcinoma - Intraosseous secondary type (dedifferentiated)

SC

Ameloblastic carcinoma - Peripheral secondary type (dedifferentiated) Primary intraosseous squamous cell carcinoma - Solid type

M AN U

Primary intraosseous squamous cell carcinoma - Derived from KCOT

Primary intraosseous squamous cell carcinoma - Derived from odontogenic cysts Clear cell odontogenic carcinoma

AC C

EP

TE D

Ghost cell odontogenic carcinoma

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

Primary intraosseous squamous cell carcinoma arising from keratocystic odontogenic tumor.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare lesion that almost exclusively occurs in the jaws. Most PIOSCCs originate from epithel...
3MB Sizes 0 Downloads 14 Views