Q U I N T E S S E N C E I N T E R N AT I O N A L

ORAL MEDICINE

Christian Bacci

A comparison between histologic and clinical diagnoses of oral lesions Christian Bacci, DDS, PhD1/Luca Donolato, DDS2/Edoardo Stellini, DDS3/Mario Berengo, MD, DDS4/ Marialuisa Valente, MD 5 Objective: The dentist has a fundamental role in the early diagnosis of lesions of the oral cavity. The aim of this study was to establish the rate of erroneous clinical diagnoses and whether a clinical diagnosis is enough. The study was conducted to ascertain the overall accuracy of clinical diagnoses established by dentists. Study design: The biopsy reports of 1,566 samples taken from 1,406 patients and examined at the Dental Outpatients Department of the University of Padua from 1 January 2006 to 30 June 2012 were analyzed in order to compare the presumptive clinical diagnosis with the final diag-

nosis based on histology. Results: Overall, the dentists’ clinical diagnoses were erroneous in 31.5% of cases. These diagnostic errors pertained to 23.8% of the benign neoplasms, 78.9% of the malignant neoplasms, and 17% of precancerous lesions. Conclusion: The present report should not be interpreted as a criticism of the clinicians making diagnostic errors but rather a confirmation of the policy to submit excised tissues for histologic examination. (Quintessence Int 2014;45:789–794; doi: 10.3290/j.qi.a32440)

Key words: clinical misdiagnosis, leukoplakia, oral cancer, oral examination, oral pathology, precancerous condition

In medicine, clinical examination has always been one of the three pillars of the diagnostic process, along with a patient’s medical history and diagnostic tests. Visual inspection is a primary diagnostic tool in dentistry and oral medicine, and the management of potentially malignant or other disorders of the oral mucosa demands 1

Consultant, Department of Neuroscience, Section of Clinical Dentistry, Unit of Oral Surgery, University of Padova, Padova, Italy.

2

Resident, Department of Neuroscience, Section of Clinical Dentistry, Unit of Oral Surgery, University of Padova, Padova, Italy.

3

Associate Professor and Head of Clinical Dentistry, Department of Neuroscience, Section of Clinical Dentistry, Unit of Oral Surgery, University of Padova, Padova, Italy.

4

Full Professor, Department of Neuroscience, Section of Clinical Dentistry, Unit of Dental Prosthesis, University of Padova, Padova, Italy.

5

Full Professor, Head of Pathology, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.

Correspondence: Dr Christian Bacci, Department of Neuroscience, Section of Clinical Dentistry, Unit of Oral Surgery, University of Padova, Padova, Italy.

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periodic visual examination. Assessing a lesion’s activity, or the outcome of treatment, and making treatment decisions often rely on clinical observation.1 The diagnostic process includes a clinical examination, followed by further investigations: the sensitivity and specificity of the former are debated in the literature.2 Approximately 5 to 15% of the general population have oral mucosal abnormalities. Without question, the vast majority of these lesions are clinically and biologically benign. The classic clinical signs of oral malignancies or premalignant lesions are well known. The problem is more a matter of inadequate clinical experience in differential diagnostics reflected in lower likelihood for the clinician to suspect cancer. Recent data also suggest that some precancerous lesions may lurk within mucosa that appears clinically normal on clinical examination alone.3

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Clinical examination clearly suffers significantly from a marked inter-observer variability when it comes to assessing lesions of the oral cavity, as well as from different conclusions being reached by a given observer (intra-observer variability) as a clinician gains experience over time.4 Unfortunately, neither Oral Medicine nor Oral Pathology are officially recognized as separate medical specialties in many countries, including Italy (although there are postgraduate specialization courses in oral surgery for DDS [Specializzazione in Chirurgia Odontostomatologica], and maxillofacial surgery for MD [Specializzazione in Chirurgia Maxillo-Facciale]). In the absence of a dedicated clinician, oral lesions may consequently be managed by oral surgeons, dentists, maxillofacial surgeons, ENT specialists, or dermatologists. Of course, when there are any doubts about the reliability of a clinical diagnosis, a biopsy should always be obtained for histopathologic examination to confirm or clarify the clinician’s impression.5 The aim of the present study was to ascertain how often clinical diagnoses prove erroneous at histology.6

METHOD AND MATERIALS A retrospective cross-sectional study was conducted on 1,813 specimens obtained from 1,406 patients examined from 1 January 2006 to 30 June 2012. Patients were examined by a clinician (dentist, oral surgeon, or maxillofacial surgeon), who established a clinical diagnosis on the basis of a physical examination (oral examination, usually associated with neck inspection and palpation). Each lesion was biopsied for histology, which generated the pathologic diagnosis. Most biopsies were handled at the Clinical Dentistry department of Padova University, some at the University’s Maxillofacial Surgery Unit, and a few at private general dental practices. The clinical diagnosis was compared with the histologic findings by two skilled pathologists dedicated to oral pathology at the Padova University Pathology Unit. If there was any doubt, a third expert’s opinion was always sought. The resulting histologic diagnosis was used to calculate how accurately the

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clinicians diagnosed the various diseases of the oral cavity.

Inclusion criteria Physical examinations of lesions of the oral cavity involving bone, connective tissue, mucous membranes, and glandular tissues were considered. The anatomical lesions were judged to be relevant if they came within the anatomical limits of the oral cavity, considered the vermilion-skin junction as the anterior limit, and the isthmus of the fauces as the posterior limit. An exception was made for the vermillion border of the lip, which was considered to all effects and purposes as a site of lesions of interest for this study although it lies outside the oral cavity.7

Exclusion criteria All reports on lesions located outside the oral cavity (as defined above) were excluded, as were reports providing insufficient detail. Many samples had been submitted for histologic examination without clear clinical details of the site involved or the appearance of the lesion, or any clinical diagnostic hypothesis, making them unsuitable for the purposes of this study.

Study design The Pathology Unit’s database was searched using “oral mucosa”, “gingival mucosa”, “vermillion”, “jaw bones”, and “lingual mucosa” as keywords, obtaining 1,813 samples (121 of which were rejected according to the exclusion criteria), which had undergone 1,582 histologic, 105 cytologic, and 21 molecular analyses. All the details in the reports meeting the inclusion criteria were input in an ad hoc database.

RESULTS The study focused on 1,566 samples. Concerning the accuracy of the clinicians’ impressions, there was no correspondence between the clinical and pathologic diagnoses in 31.5% of cases. The clinical diagnosis proved inaccurate in 23.8% of cases of benign lesions, and for malignancies the percentage was as high as

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78.9% inaccuracy. The clinical diagnosis was erroneous for 17% of the cases of precancerous lesions, and for 21.3% of the cases of lichen planus. Cases of pemphigus and mucous membrane pemphigoid (confirmed by immunofluorescence) were always diagnosed correctly. As for the radiolucent bone lesions, the diagnosis was erroneous in 17.6% of the cases initially identified by the clinician as cysts, and 57.4% of those diagnosed as apical granulomas. Among 71 cases considered as dentigerous cysts (according to the WHO classification of 1992), only 10% were erroneously diagnosed.8 There were seven cases of pseudocyst, all diagnosed correctly on clinical examination (three simple bone cysts and four aneurysmal bone cysts). Among the pigmented lesions, the clinical diagnoses proved erroneous for 28.6% of the amalgam tattoos, 40% of the nevi, and 70% of the hemangiomas. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) and candidiasis were never misdiagnosed. Figure 1 shows which conditions were most frequently misdiagnosed, while Table 1 shows the number of samples considered, the number of erroneous clinical diagnoses, and the rate of error for each condition. Table 2 shows the rate of erroneous diagnoses by anatomical site: only 1,285 samples were considered in terms of the anatomical distribution of the sampling sites, because this information was lacking for the other 281 samples.

DISCUSSION The high rate of erroneous clinical diagnoses emerging from this study shows that clinical examination alone leads to a misdiagnosis in about one in three cases. This can be a serious matter, especially given the high frequency of error in the case of malignancies. Malignancies may appear as nonspecific morphologic features and be described as ulcers, erosions, or hardened plaque, possibly arousing suspicions, but hardly enabling a reliable diagnosis. There were few erroneous diagnoses of benign neoplasms in comparison with other types of lesion, prob-

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10% 18% 3% 4% 4% 5% 16% 6%

9% 13% 12% malignant tumor hemangiomas apical granuloma hyperkeratosis nevi amalgam tattoo Fig 1

benign tumor cyst precancerous lesions autoimmune pathology others

Most commonly misdiagnosed conditions.

ably because these conditions were mainly of viral or traumatic origin, such as papillomas or fibro-epithelial polyps, respectively lesions with characteristic features and sites that make them easier to identify. Precancerous lesions were also detected fairly easily, though in some cases even the most experienced eye would be unable to identify them accurately. Only histology can distinguish between different degrees of epithelial dysplasia in apparently innocuous lesions (this was true of 10 lesions in the series, ie about 10% of all precancerous lesions). On the other hand, some lesions were easily identified clinically, while histology showed very nonspecific alterations. Pemphigus and mucous membrane pemphigoid were always diagnosed correctly in the series (as confirmed by immunofluorescence), possibly due to the limited number of cases involved, while the findings on diagnostic errors relating to oral lichen planus (Fig 2) are due to an inappropriate use of the term “leukoplakia” to indicate whole white patches, or to lesions being

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Table 1

Number of samples, number of erroneous clinical diagnoses, and error rate for each condition

Conditions

Histologic diagnoses

Malignant tumor Benign tumor Precancerous lesions

Autoimmune disease

Erroneous clinical diagnoses

Rate (%)

38

30

78.9

277

66

23.8

100

17

17.0

Total

429

148

34.5

Lichen planus

141

30

21.3

1

0

0.0 0.0

Pemphigoid Pemphigus

6

0

85

3

3.5

Total

267

47

17.6

Inflammatory odontogenic cyst

162

28

17.3

Dysembryonic odontogenic cyst

97

16

16.5

8

3

37.5

7

0

0.0

148

85

57.4

Nevi

10

4

40.0

Amalgam tattoo

14

4

28.6

Hemangiomas

10

7

70.0

BRONJ

15

0

0.0

Candidiasis

30

0

0.0

Hyperkeratosis

26

14

53.8

Sjogren’s syndrome

Cyst

Non-odontogenic cyst Pseudocyst Apical granuloma

Table 2

Rate of erroneous diagnoses by anatomical site

Anatomical sites Upper lip - vermillion-skin junction Upper lip - inner mucosa Lower lip - vermillion-skin junction Lower lip - inner mucosa Alveolar mucosa

Histological diagnoses

Erroneous clinical diagnoses

Rate (%)

7

3

42.9

11

4

36.4

3

2

66.7

121

31

25.6

44

18

40.9

Gingiva

261

74

28.4

Buccal mucosa

145

27

18.6

Dorsal tongue

68

26

38.2

Ventral tongue

14

5

35.7

Lateral tongue

27

12

44.4

Hard palate

89

34

38.2

Soft palate

11

0

0.0

Floor of mouth

25

12

48.0

Retromolar trigone

52

19

36.5

Lower jaw bone

196

47

24.0

Upper jaw bone

183

65

35.5

8

3

37.5

Maxillary sinus

18

7

38.9

Tonsillar pillars

2

1

50.0

Labial commissure

792

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a Figs 2a and 2b

b Clinical (a) and pathologic (b) findings in lichen planus (hematoxylin–eosin, 20×).

a Figs 3a and 3b

b Clinical (a) and pathologic (b) findings in amalgam tattoo (hematoxylin–eosin, 40×).

confused with a mucous membrane pemphigoid (though this only applied to 6% of all diagnoses of oral lichen planus). Cysts of inflammatory origin were more frequently confused with apical granulomas, and vice versa. A glance at the rate of erroneous diagnoses for apical granulomas shows that almost two in three diagnoses were erroneous; radiography and even surgical procedures did not allow distinction between these two conditions. There were about one in three misdiagnoses of nonodontogenic cysts, but the limited number of cases involved probably means that this finding is not generalizable. The diagnoses of BRONJ were always accurate, but this is always an essentially clinical diagnosis; the pathologist can only identify the process in the sample and assess the bone necrosis underway, or a bacterial superinfection at most, without knowing the cause of the process, given that bone necrosis induced by radia-

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tion therapy has the same histologic features as BRONJ, apart from any metastases. When it came to the pigmented lesions, the most commonly seen were amalgam tattoos (Fig 3), which were misdiagnosed in about one in four cases. This kind of lesion is easier to identify correctly if it lies close to the site of an amalgam filling, which may even have recently been removed (facilitating the metallic pigments’ penetration in the oral mucosa). A relatively high rate of clinical diagnostic errors was found regarding nevi (often confused with amalgam tattoos), even higher than for hemangiomas (confused not only with amalgam tattoos, but also with benign fibro-epithelial tumors and mucoceles). Finally, when frictional hyperkeratosis was considered, approximately one in two cases were misdiagnosed. A study conducted by Kondori et al5 in 2011 identified misdiagnoses in 43% of cases, these misdiagnoses being made by general dentists in 45.9% of cases, by

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a Figs 4a and 4b

b Clinical (a) and pathologic (b) findings in squamous carcinoma (hematoxylin–eosin, 10×).

maxillofacial surgeons in 42.3%, by endodontists in 42.2%, and by periodontists in 41.2%. In the present larger sample, the results support Kondori’s conclusion that all excised tissues should be sent to the pathologist for analysis because the rates of diagnostic error are high. Another study with a similar design to the present study was published in 2011 by Patel et al,2 who found a moderate correlation between clinical diagnoses and histologic diagnoses, measured at 50.6%; in the present sample, this correlation reached 68.5% (keeping in mind that concordance was only 21.1% for malignant lesions). An example of an oral cancer is reported in Fig 4.

CONCLUSION The goal of the present study was not to criticize clinicians for making diagnostic errors, but to emphasize the importance of submitting all excised tissue for histopathologic examination. Our attention was focused not on how more or less skilled clinicians (be they oral surgeons, dentists, maxillofacial surgeons, ENT specialists, or dermatologists) might arrive at a more accurate clinical diagnosis, but on providing a thorough description of the situation on the strength of a large case sample. Greater attention should be paid to improving communications between clinicians and pathologists regarding the clinical information provided by the former on lesions submitted to the latter for examination,

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and on the use of precise and appropriate terms to describe them. An accurate description can only facilitate the subsequent histologic assessment. These results are interesting for the general practitioner. As recommended previously,2,5 all excised tissues should be send for histologic examination.

REFERENCES 1. Reichart PA, Philipsen HP. Oral erythroplakia – a review. Oral Oncol 2005;41:551–561. 2. Patel KJ, De Silva HL, Tong DC, Love RM. Concordance between clinical and histopathologic diagnoses of oral mucosal lesions. J Oral Maxillofac Surg 2011;69:125–133. 3. Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 2008;44:10–22. 4. Zadik Y, Orbach H, Panzok A, Smith Y, Czerninski R. Evaluation of oral mucosal diseases: inter- and intra-observer analyses. J Oral Pathol Med 2012;41:68–72. 5. Kondori I, Mottin RW, Laskin DM. Accuracy of dentists in the clinical diagnosis of oral lesions. Quintessence Int 2011;42:575–577. 6. Richards D. Clinical recommendations for oral cancer screening. Evid Based Dent 2010;11(4):101–102. 7. Mallia RJ, Thomas SS, Mathews A, et al. Laser-induced autofluorescence spectral ratio reference standard for early discrimination of oral cancer. Cancer 2008;112:1503–1512. 8. Kramer IRH, Pindborg JJ, Shear M. Histological Typing of Odontogenic Tumours. Geneva: Springer-Verlag, 1992.

VOLUME 45 • NUMBER 9 • OCTOBER 2014

A comparison between histologic and clinical diagnoses of oral lesions.

The dentist has a fundamental role in the early diagnosis of lesions of the oral cavity. The aim of this study was to establish the rate of erroneous ...
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