By Mark Tuffley, BDSc (Hons) (Qld), MB BS (Qld), MDSc

In this article, we present a complex case of leukoplakia progressing to early squamous cell carcinoma and it’s effective surgical management with Geistlich Mucograft combined with Complex Nutritional Metabolite (CNM) antiseptic wound dressings.

Case presentation
A 42-year-old female was referred by her medical practitioner in February 2013 for assessment and management of an area of leukoplakia, left ventral surface of the tongue (Figure 1).

Salient points in the medical history are:
1. No history of smoking, minimal alcohol intake and no illicit drug use;and
2. Medications:
a. Clomipramine (tricyclic medication to assist management of OCD);
b. Symbicort turbuhaler 200 /6 mcg;
c. Salbutamol inhaler;
d. Microgynon 30 ED; and
e. Thyroxine.

Comment: Clomipramine is known to induce twitching of the tongue with dystonia and rhythmic movements, in addition to a dry mouth. To counter the relative xerostomia, the patient had been in the habit of sucking on mint lozenges – this was subsequently changed to sugar free chewing gum.

The patient was observed to have fasciculating and involuntary movements of her tongue.

The patient was seen regularly since the initial referral. The propensity to recur following tradition biopsy techniques was a matter of concern, suggestive of a progressive mutative “field change” with ongoing and overlapping cellular dysmorphisms.

The progression to severe dysplasia with a focus of minimally invasive squamous cell carcinoma is demonstrated in Figures 2 to 5 (Comment: Leukoplakia is an idiopathic, potentially premalignant lesion (PML) of the oral cavity; erythroleukoplakia,
demonstrating both hyperkeratosis and mucosal atrophy is more strongly associated with dysplasia and progression to malignancy, as observed in this case).

leukoplakia-diagram-1

Other white lesions such as Candidiasis, frictional and chemical keratoses including nicotine, areca nut and probably habitual lozenge mucosal contact in addition to autoimmune processes such as lichen planus and lichenoid plaques with, for example lupus erythematosis may be present with PMLs as also seen in this case.

The response to therapeutic strategies often indicates the underlying cellular behaviour, however biopsy and histological examination remains the gold standard of diagnosis and management.1 Despite all efforts to modify contributing factors e.g. smoothing the lingual aspect of the lower left posterior teeth, eliminating the habitual use of mint lozenges and strict oral hygiene following the use of oral steroid bronchodilator inhalations, over time it was clear that the prospect of eliminating involuntary trauma from the adjacent teeth may be required; this was regrettably completed in May 2016 (Figure 6).

Wider excision of the previously diagnosed severe dysplasia and focal squamous cell carcinoma was undertaken and Geistlich Mucograft was sutured to excisional base with slight overlap of the surgical margins (Geistlich Mucograft is a unique 3D collagen matrix designed specifically for soft-tissue regeneration in the oral cavity).

Additionally, the site was treated with Complex Nutritional Metabolites (CNM). CNMs, when applied to tissues, create nutrient enriched metabolomes. It has been described as direct parenteral nutrition for tissues and
“comfort food” for stressed cells.

This is known from a landmark study in 2007 where CNMs were applied to activated (“angry”) macrophages in vitro with a 50% reduction of the M1 cytokine expression being consistently detected.

Clinically, this effect appears to reflect a switching to M2, proresolution healing. These findings confirm current pro-resolution research findings and healing paradigms; the broader use of CNMs has implications for wound dressing strategies generally.2,3

The initial healing was only accompanied with very little inflammatory response and excellent wound healing (Figure 7). The patient also reported minimal use of analgesic medications in contrast to previous biopsy procedures. Follow ups after 1 and 3 months showed formation of smooth and resilient tissue (Figures 8 & 9).

leukoplakia-diagram-2

Despite the field change which occurs with leukoplakia, no evidence of marginal recurrence is evident so far although careful ongoing observation is clearly required.

Conclusion
Grafting with Geistlich Mucograft combined with CNM antiseptic wound dressings appears to advantage anatomical restoration of the area without undue fibrosis and tethering. Additionally, tissue stability as well as improved pain profiling are also observed. Geistlich Mucograft can therefore be recommended as an effective treatment modality for the repair of denuded areas within the oral cavity.

References
1. Dost, F., LeCao, K., Ford, P.L. et al., Malignant transformation of oral epithelial dysplasia: a real world evaluation of histopathologic grading. Oral Surg Oral med Oral Pathol Oral Radiol; 2013 Oct 17 Epub.
2. Serhan, C,N., Pro-resolving lipid mediators are leads for resolution physiology. Nature 2014; 510: 92-101.
3. Serhan, C.N., Brain, S.D., Buckley, C.N. et al., Resolution of inflammation, state of the art, definitions and terms. FASEB Journal 2007; 21: 325-332.

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