1. Pseudoepitheliomatous hyperplasia (PEH) in BRONJ
Jerry Bouquot,* Douglas Gnepp,**
Patricia Suarez,* Shaolei Lu *
* University of Texas, Houston, USA
** Brown University, Providence, Rhode Island, USA
Pseudoepitheliomatous hyperplasia (PEH) in BRONJ
may mimic squamous cell carcinoma
J. E. Bouquot, DDS, MSD, FICD, FACD, FADI, FRCM (London)
Professor & Chair, Department of Diagnostic & Biomedical Sciences
University of Texas School of Dentistry at Houston, Room 5460
7500 Cambridge Street, Houston, TX 77054

2. Dr. Bouquot, Oral Cancer, Precancer
J.E. Bouquot, DDS, MSD, FAAOMP, Diplomate-ABOMP, FICD, FADI, FACD, FRSM
1945
1946
1947
1949
1954
With brothers Dave, Randy, Den
With father Elmer
With sisters Jan, Marlene
With mother Marion
With brother Dave
1963
1967
1969
2000
2012
High school grad,
Caldwell, New Jersey
College grad.
Northfield, Minnesota
With mother Marion,
at Univ. Minnesota
Director of Research, MFCenter, WV
University of Texas; this is what 45 years in dentistry will do to you

3. Dr. Bouquot, Oral Cancer, Precancer
Fall, 2011

4. Most Popular Oral Pathology Presentations in the World
The Bouquot-To-Go (BTG) disk An oral disease resource, developed by Dr. J. E. Bouquot, USA
Most Popular Oral Pathology
Presentations in the World
This disk, first made available in 2002, has more than 3,000 clinical and microscopic photos in Power Point 2010 format, usually with hyperlinks. It is continuously updated and all photos are copyright free.
The 53 Most Common Oral Lesions. Hyperlink handout; 500+ clinical photos; first version: 2002
The Must-Know Oral Lesions. Hyperlink handout in differential diagnosis; 720+ clinical photos; first version: 2009
The Beginnings of Oral Pathology/Oral Medicine, 1805-
PP presentation depicting the earliest books, articles,
drawings of oral lesions; 90+ photos; first version: 2002
The CD Johnson Collection – A potpourri of Oral Lesions
from the Urgent Care Clinic. Hyperlink handout of various
oral lesions, especially those related to drug use; 500+ clinical
photos; first version: 2009
The Dreizen Collection – Oral Lesions from the University
of Texas, Houston, One of the first popular collections
of oral clinical lesions, from a previous University of Texas
faculty member; 90+ clinical photos; first PP version: 2009
Ischemic Jawbone Disease. Hyperlink handout providing
very detailed information about ischemic and inflammatory
jaw disorders; 1,000+ photomics and clinical photos; first
version: 2006
Review of NICO. PP of a popular lecture; 150+ photos; first
version: 2003
The Little Book of Lists. Hyperlink handout of those
important lists of oral lesions/ effects associated with drugs,
syndromes, systemic disorders, etc.; first version: 2009

5. Pseudoepitheliomatous Hyperplasia
in BRONJ
The Problem

6. PEH in BRONJ The Problem: Alveolar Epithelium is Very Proliferative
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ The Problem: Alveolar Epithelium is Very Proliferative
Odontogenic and alveolar/gingival epithelium has a very strong tendency to produce long rete processes which in other sites might be interpreted as “invasion”
Inflamed mucosa at edge of BRONJ (Bisphosphonate Related Osteonecrosis of the Jaws) is often very proliferative
This may be mistaken for carcinoma
Gingivitis
Gingivitis
Oral pathologists are familiar with this phenomenon; not so for medical pathologists
Proliferative Epithelium
of Marginal Gingiva
Periapical Cyst

7. PEH in BRONJ The Problem: Odontogenic Epithelium is Very Proliferative
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ The Problem: Odontogenic Epithelium is Very Proliferative
Subacute Gingivitis
Periapical Cyst

8. PEH in BRONJ The Problem: Alveolar Epithelium Entraps Bone
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ The Problem: Alveolar Epithelium Entraps Bone
Chronic Gingivitis with Entrapped Bone Fragment v

9. PEH in BRONJ The Problem: Proliferative Epithelium Engulfs Bone
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ The Problem: Proliferative Epithelium Engulfs Bone v
Chronic Gingivitis with Entrapped Bone Fragment

10. PEH in BRONJ The Problem: Proliferative Epithelium Near BRONJ Bone
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ The Problem: Proliferative Epithelium Near BRONJ Bone
Proliferating, degenerated epithelium may look ominous because it is not expected in osteonecrosis; also, it is known that carcinoma can develop at openings of draining osteomyelitis in long bones

11. Pseudoepitheliomatous Hyperplasia
in BRONJ
Study Design

12. PEH in BRONJ Objective, Study Design: A Biopsy Service Series
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Objective, Study Design: A Biopsy Service Series
Objective:
To characterize pseudoepitheliomatous hyperplasia (PEH) in bisphosphonate-related osteonecrosis of the jaws (BRONJ)
Study Design:
A convenience sample
-- Referral biases are unknown
Cases were identified from 89 BRONJ biopsies in two surgical pathology services (4 cases were consults)
Exclusion criteria: poor records
BRONJ
BRONJ (from above case)

13. Pseudoepitheliomatous Hyperplasia
in BRONJ
Results

14. PEH in BRONJ Results: 13 Examples of PEH Amongst 89 BRONJ Cases
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: 13 Examples of PEH Amongst 89 BRONJ Cases
13 cases (14.6%) identified from 89 BRONJ cases
9 (69.2%) used IV, 5 used oral bisphosphonates
8 (61.5%) were females
Average age at diagnosis: 63 years (range: 54-79)
4 (30.8%) with actinomycosis
4 (30.8%) cases: prior suspicion of squamous cell carcinoma
Exposed bone in BRONJ
© Clinical photo: Dr. John Hellstein, University of Iowa

15. PEH in BRONJ Results: Histopathology of BRONJ
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of BRONJ
All cases: subacute inflammation, bony sequestra with resorption lacunae, osteoclasts (maybe), bacterial colonies

16. PEH in BRONJ Results: Histopathology of BRONJ
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of BRONJ
13 (100%): inflammatory cells
13 (100%): granulation tissue
5 (38.5%): fibrous tissue
2 (15.4%) with osteocytes
1 (7.7%) with osteoclasts
Osteoclasts
Resorption lacunae with occasional osteocytes

17. PEH in BRONJ Results: Histopathology of Ulcer Margin
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Ulcer Margin
All cases: epithelial proliferation and subacute inflammation of mucosa at margin of exposed bone

18. PEH in BRONJ Results: Histopathology of Marginal Epithelium
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Marginal Epithelium
8 (61.5%): very degenerated proliferating epithelium; much like lining of periapical cyst

19. PEH in BRONJ Results: Histopathology of Marginal Epithelium
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Marginal Epithelium
Proliferation of surface epithelium overlying bony sequestra

20. PEH in BRONJ Results: Histopathology of Proliferating Epithelium
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Proliferating Epithelium
7 (53.9%): epithelium immediately adjacent to bony sequestra; no entrapment of bone

21. PEH in BRONJ Results: Histopathology of Proliferating Epithelium
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Proliferating Epithelium
Inflammation and proliferation epithelium adjacent to bony sequestra, maybe filling resorption lacunae

22. PEH in BRONJ Results: Histopathology of Entrapped Bone
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Entrapped Bone
Multiple sequestra entrapped by epithelium

23. PEH in BRONJ Results: Histopathology of Entrapped Bone
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Entrapped Bone
5 (38.5%): bony sequestrum completely surrounded by epithelium, with occasional dark, somewhat enlarged nuclei in 2 (15.4%)

24. PEH in BRONJ Results: Histopathology of Proliferating Epithelium
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Proliferating Epithelium
2 (15.4%): massive epithelial proliferation filling medullary spaces

25. PEH in BRONJ Results: Histopathology of Entrapped Bone
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Results: Histopathology of Entrapped Bone
Degenerated epithelium filling medullary spaces and entrapping bone
Resorption lacunae filled with epithelium mimics destruction by squamous cell carcinoma

26. Pseudoepitheliomatous Hyperplasia
in BRONJ
Discussion

27. PEH in BRONJ Discussion: PEH Reports with Jawbone Associations
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Discussion: PEH Reports with Jawbone Associations
Potential look-alikes:
Squamous odontogenic tumor
Odontogenic hamartoma
Squamous cell carcinoma, including primary intraosseous types
Primary intraosseous mucoepid. carcinoma
PEH with jawbone fragments has been reported previously:
Chronic osteomyelitis with augmentation bone (n = 2; Warter, et al, 2000)
5 of 8 BRONJ cases (Hansen, et al, 2006)
7 of 10 osteoradionecrosis (ONJ) cases (Hansen, et al, 2006)
4 of 15 BRONJ cases (Bouquot, Gnepp, 2009, AAOMP abstract)
Frequent in BRONJ and ONJ in rats (Hokugo, et al, 2010)

28. Conclusions Conclusions Pseudoepitheliomatous Hyperplasia
in BRONJ
Pseudoepitheliomatous Hyperplasia
in BRONJ
Conclusions
Conclusions

29. PEH in BRONJ Conclusions:
© J.E. Bouquot,, University of Texas; Houston, USA; presented at 16th Biennial IAOP Congress, São Pedro, SP, Brasil, 2012
PEH in BRONJ Conclusions:
Pathologists should be aware of this proliferative phenomenon so as not to misdiagnose it as squamous cell carcinoma
BRONJ-associated PEH must be ruled out before a carcinoma diagnosis can be applied to a BRONJ lesion
© Right photo: Dr. K. Gundlach, University of Rostock, Germany

30. A newfound family? The Roberto Bouquot clan of Argentina
©Photo(s): Facebook, Roberto Bouquot
A newfound family? The Roberto Bouquot clan of Argentina