International Journal of Oral and Maxillofacial Pathology

Bevel: Case Report

Neurofibromatosis Type-1 with Solitary Neurofibroma of Palate: A Rare Case with Literature Review

Yeluri Sivaranjani, Chittemsetti Samatha, Taneeru Sravya, Rajani Korlepara

Abstract

Neurofibromatosis is a genetic disease characterised by multiple neurofibromas usually inherited as an autosomal dominant variety. Neurofibroma is a neurogenic tumour which manifests either as a solitary nodule or multiple as a part of neurofibromatosis. Skin is the most common site of involvement and its presence in oral cavity is rare. Oral manifestations have been reported in only 4-7% of neurofibromatosis cases. The most commonly affected sites include tongue and buccal mucosa and the rare sites of occurrence being palate and maxillary-mandibular bones. This article presents a rare case of multiple neurofibromatosis associated with a solitary neurofibroma of the palate in a 60 year old female.

 

Key Words: Hard Palate;Maxillary;Neurofibromatosis;Neurofibroma.

 

Yeluri Sivaranjani, Chittemsetti Samatha, Taneeru Sravya, Rajani Korlepara. Neurofibromatosis Type-1 with Solitary Neurofibroma of Palate: A Rare Case with Literature Review. International Journal of Oral & Maxillofacial Pathology; 2015:6(1):30-34. © International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved.

 


Introduction

Neurofibroma is the most frequent benign tumour of nerve tissue origin, derived from the cells of nerve sheath.1 Holt defined it as “A hereditary hamartomatous disorder, probably of neural crest origin, involving not only neuroectoderm but also endoderm, with the potential of appearing in any organ system of the body”.2 According to the classification given by Shklar and Meyer in 1963, it may present either as a solitary or multiple lesion as a part of generalised syndrome of Neurofibromatosis(NF).3 NF differs from the solitary form only with respect to systemic and hereditary factors.1 Though several clinical phenotypes are recognised in NF, NF-1 is the most common accounting for about 90% of cases. Mutations have been discovered on the long arm of chromosome 17 (17q11.2) with aberrations in neurofibromin, the protein product of the NF1 gene.4

 

NF1 occurs with a frequency of one case in approximately 3,000 individuals. The incidence and prevalence of NF1 lies between 1 in 2,500–3,300 and 1 in 5,000 individuals respectively. It is characterized by an autosomal dominant inheritance with complete penetrance but variable expression.1 NF 1 was first described by Robert William smith in 18495 and later classic description was given by Friedrich Daniel von Recklinghausen, in 1882 and hence it is referred to as von Recklinghausen’s disease.6

 

The most frequent site of oral neurofibromatosis is the tongue followed by the oral mucosa and floor of the mouth. Palate and maxillary-mandibular bones are considered to be rare sites for the occurrence of the disease.7 In this regard, a rare case of NF-1 associated with solitary neurofibroma of palate was reported in a 60 year old female patient.

 

Case Report:

A 60 year old female presented with swelling on the hard palate since four years. Initially the swelling was peanut in size which gradually increased to the present size and was associated with difficulty in phonation. Patient also gave the history of multiple nodules of varying size all over body since 50 years. Past medical and dental history were non-contributory. Positive family history with similar clinical manifestations was noticed.

 

General physical examination disclosed hyperpigmented dome-shaped nodules and café-au-lait spots of varying diameters with smooth edges. On inspection multiple nodules are seen with extensive involvement of trunk, face, extremities and the size of the lesions varied from few millimetres to several centimetres which are brownish black in color with well-defined margins. On palpation, all the inspectory findings were confirmed and the nodules were soft to firm in consistency, non-fluctuating, smooth, sessile andnon-tender.(Figure 1a)

 

Intraoral examination revealed a solitary, well defined, nodule with brown pigmentation in the midline of anterior portion of the hard palate measuring approximately 1 to 1.5 cm in diameter. (Figure 1b) On palpation, all the inspectory findings were confirmed and the lesion was sessile, compressible and soft in consistency with smooth surface. As a part of routine investigations, panoramic radiograph was taken which did not reveal any bone involvement. Based on clinical presentation of the multiple pigmented skin nodules and family history of first-degree relative, a provisional diagnosis of NF-1 with neurofibroma was given. Schwannoma, traumatic neuroma were considered in the clinical differential diagnosis.

An excisional biopsy was performed and sent for histopathological examination. Grossly the specimen was creamish brown measuring approximately 1X1.5 cm and is roughly oval in shape with well-defined margins and on palpation it was soft to firm in consistency with smooth surface.(Figure 1c) Microscopic examination revealed well circumscribed lesion with surface epithelium and the underlying connective tissue.(Figure 2a&b) Stroma showed numerous elongated spindle shaped cells with wavy serpentine dark staining nuclei. (Figure 2c&d) These cells were interlaced with dense bundles of collagen fibres. Numerous mast cells were scattered throughout stroma. Abundant vascularity and inflammatory cells predominantly lymphocytes were evident.


Description: Macintosh HD:Users:madhusudanastekar:Desktop:Astekar's:ijomp.org:New Submissions:00. PAYMENT RECEIVED:Pending 842. CR. Neurofibromatosis type-1-Samata:842-4594-1-SP.jpg

Figure 1:Diffuse multiple brownish black pigmented nodules on the face(a).Well defined solitary nodule on the anterior aspect of the hard palate (b).Excised specimen(c).

Description: figure 2

Figure 2: Photomicrograph of hematoxylin and eosin stained section illustrating well circumscribed lesion with epithelium and the underlying connective tissue stroma. In low (a) and high power view (b). Numerous elongated spindle shaped cells with wavy serpentine dark staining nuclei within the connective tissue stroma at low (c) and high owere view (d).

 


Special stain was performed with toluidine blue which revealed numerous spindle to oval shaped cells showing purplish red granules in the cytoplasm and nuclei exhibiting sky blue colour resembling mast cells.(Figure 3) Further, immunohisto-chemistry revealed S-100 positive cells all over the lesional area indicating its neural origin.(Figure 4a&b) Depending on all the above findings, a final diagnosis of NF-1 associated with solitary neurofibroma of palate was made. Follow up of the patient was done and no recurrence was noticed as far.

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Figure 3: Photomicrograph showing abundant mast cells. (x400;  Toluidine blue)

 

Discussion:

Neurofibroma is characterized by mixture of Schwann cells, perineurial cells and endoneurial fibroblasts. The World Health Organisation has subdivided neurofibromas into dermal and plexiform types. The uncommon variant of neurofibroma is the diffuse neurofibroma which typically involves the skin and subcutaneous tissue.8 Neurofibromas may reach a very large size without causing apparent discomfort to the patient. The presence of neurofibroma is the hall mark of NF-1 and is considered to be one of the clinical criteria aiding in diagnosing NF-1.9

 

Neurofibromatosis in humans primarily affects cell growth of neural tissues with basic defect in embryonic neural crest cells. Many theories have been proposed to explain the etiology and pathogenesis of multiple neurofibromatosis. They include infectious theory, toxic theory, insufficiency of endocrine glands, ectodermal theory, mesodermal theory, and teratologic theory.10 A leading theory is that the NF1 gene functions as a tumor suppressor and neurofibromin, NF1 gene product is a negative regulator of the Ras oncogene and plays a role in intracellular signalling. When its expression is lost by mutation, Ras remains active and promotes cell proliferation and tumor growth.11

 

Despite the advances of molecular biology, the diagnosis of NF1 is still based on clinical criteria given by National Institute of Health Consensus Development Conference (NIHCDC), at least two of the following criteria (Table 1) must be present to make the diagnosis of NF-1.12 The present case satisfies 1, 2, 7 of the below mentioned criteria.


Description: C:\Users\samat\Desktop\figure 4.jpg

Figure 4: Photomicrograph showing S-100 positive cells (a) magnification x100; IHC stain (b) magnification x400; IHC stain.

 


Pigmented lesions of NF-1 usually appear as café-au-lait spots and freckles. These are frequently present at birth or may appear during the first years of life. The colour varies from yellowish to dark brown and these macules are oval shaped with smooth regular borders typically known as coast line of California.4 Clinical appearance of cutaneous neurofibromas varies from small papules to larger soft nodules to massive baggy, pendulous masses (elephantiasis neuromatosa). They may be present at birth, but they often begin to appear during puberty and may continue to develop slowly throughout adulthood.13 NF-1 has been reported in all races, with no definite sex predilection. Intraorally, the tongue is the most common site followed by lips, buccal mucosa, gingiva, floor of the mouth, palate. Enlargement of fungiform papillae was the most common oral finding (53%), followed by intraoral neurofibromas (26%).13 Table-2 summarizes the previously reported cases of NF-1 associated with neurofibroma of palate. Occasionally neurofibromas are located within the jaws mostly in the mandible, associated with the mandibular nerve. Radiographic findings include enlargement of the mandibular foramen, enlargement or branching of the mandibular canal, increased bone density.13 The present case did not reveal any such radiographic findings.


Sl. No.

Criteria

1

Five or more cafe-au-lait spots larger than 5 mm in diameter in prepubertal patients; six or more cafe-au-lait spots larger than 15 mm in diameter in postpubertal patients

2

Two or more neurofibromas of any type, or one plexiform neurofibroma

3

Axillary or inguinal freckling

4

Optic glioma

5

Two or more Lisch’s nodules

6

A distinctive osseous lesion (pseudoarthrosis of the tibia or sphenoid wing dysplasia)

7

A first-degree relative diagnosed with NF-1 in accordance with the above criteria.

Table 1: The diagnostic criteria by National Institute of Health Consensus Development Conference.


 

 


Reference

Cases

Age Range (years)

Gender (M:F)

Occurrence on palate

Borberg A et al14 (1951)

5

-

-

Solitary – 2

Preston F W et al15 (1952)

4

-

-

Solitary -1

Hankey G T16 (1933)

1

44

Female

Solitary -1

Baden E et al10 (1955)

43

3-68

23:20

Solitary - 6

Baden et al9 (1963)

1

34

Female

Solitary – 1

Miles D A et al17 (1986)

1

35

Male

Solitary – 1

Anand Kumar C et al18 (2011)

1

65

Male

multiple nodules

Jouhilahti EM et al19 (2012)

103

3-73

48:55

Solitary – 15

Bharath TS et al20 (2014)

1

38

Female

Solitary – 1

Table 2: Review of previously reported cases of NF-1 associated with palate

 


Tumour

Type

Histopathology

IHC

S100

EMA

CD34

Neurofibroma

Non-encapsulated

Mixture of Schwann cells, perineurial cells and endoneurial fibroblasts.

+

+

+

Schwannoma

Encapsulated

Schwann cells: cellular palisaded pattern (Antoni type A) and a loose paucicellular pattern (Antoni type B)

+++

++

++

Granular Cell Tumor

 

Round or polygonal cells with small nuclei and abundant granular cytoplasm.

++

-

-

Traumatic Neuroma

Encapsulated

Proliferation of both Schwann cells and axons.

+

-

+

PEN

++

-

+

Perineurioma

Non-encapsulated

Elongated spindle cells presenting bipolar cytoplasmic processes, fusiform nuclei and eosinophilic cytoplasm disposed embedded in a mixed collagenous and myxoid stroma

-

+

-

Table 3: Differential diagnosis21

 


Neurofibromas should be differentiated from Schwannoma, Granular cell tumor, Traumatic neuroma, Palisaded encapsulated neuroma (PEN) and Perineurioma21(Table-3). Tuberous sclerosis must also be considered when patient presents with multiple cutaneous nodules and oral soft tissue swellings.17 Solitary neurofibroma and neurofibromas associated with NF-1 has to be distinguished as there is difference in clinical behaviour, treatment, and prognosis. The recurrence is seen in 20% of the cases after complete resection and may be up to 44% with subtotal resection.20

 

Besides cosmetic concern, greater clinical significance of NF-1 lies in its malignant transformation. The most common malignancy associated with NF-1 is malignant peripheral nerve sheath tumour which has been reported to occur in 5-15% of cases with poor prognosis and 5 year survival rate of only 15%.4 Hence, long term review of patients is essential as there is a definite risk of malignant transformation.

Conclusion

NF-1 presents with significant oral manifestations hence, dentists should be aware of this disorder which will help in timely diagnosis and treatment. As this is a progressive disease with definite risk of malignant transformation, lifelong evaluation of the patients for newly forming or pre-existing lesions is essential.

 

Acknowledgement

We would like to thank the staff members from the Department of Oral and Maxillofacial Pathology for their support.

 

Author Affiliations

1.Dr.Yeluri Sivaranjani, Professor, 2.Dr.Chittemsetti Samatha, Post Graduate Student, 3.Dr.Taneeru Sravya, Senior lecturer, 4.Dr.Rajani Korlepara, Senior lecturer, Department of Oral Pathology, Mamata Dental College, Khammam, Andhra Pradesh, India.

 

References:

1.   Shafer W, Hine L , Levy. Text book of Oral pathology. 7th edition. Elseivier; New Delhi: 2012. p 202-3.

2.   Holt JF. Neurofibromatosis in children. Am J Roentgenol 1978;130(4):615-39.

3.   Shklar G, Meyer I. Neurogenic Tumours of the Mouth and Jaws. Oral Surg Oral Med Oral Pathol 1963;16(9):1075-93.

4.   Rupak S, Baby GG, Padiyath S, Kiran Kumar KR. Neurofibromatosis Type I with oral manifestations. e-Journal of Dentistry 2012;2(1):136-9.

5.   Kobrin JL, Blodi FC, Weingeist TA. Ocular and orbital manifestations of neurofibromatosis. Surv Ophthalmol 1979;24:45-51.

6.   Von Recklinghausen FD: On Multiple Fibromas in the Skin and their Relationship to Multiple Neuromas. Berlin; Hirschwald: 1882.

7.   Munhoz EA, Cardoso CL, Tolentino ES, et al. Von Recklinghausen's disease - Diagnosis from oral lesion: Neurofibromatosis I. Int J Odontostomat 2010;4(2):179-83.

8.   Pukara MM, Pukara SM, Borole BS. Huge solitary neurofibroma of the oral cavity a case report. J Oral Maxillofac Surg Med Pathol 2014;26:96–7.

9.   Baden E, Teaneck NJ, Fischer RJ, Trenton NJ. Multiple neurofibromatosis and neurofibroma of the palate. Report of a Case. Oral Surg Oral Med Oral Pathol 1963;16:1356-64.

10.           Baden E, Pierce HE, Jack̀son WF. Multiple neurofibromatosis with oral lesions. Oral Surg Oral Med Oral Pathol 1955;8(3):263-80.

11.           Gutmann DH. The neurofibromatoses: when less is more. Hum Mol Genet 2001;10:749.

12.           National Institutes of Health Consensus Development Conference: Neurofibromatosis. Arch Neurol Chicago 1988;45:575-79.

13.           Neville WB, Damm D, Allen CM, Bouquot JE. Oral and maxillofacial pathology. 3rd Edition. Elseivier; Philadelphia; 2010. p 529-31.

14.           Borberg A. Tuberous sclerosis and Recklinghausens neurofibromatosis. Acta Psychiatr Neural Stand 1951;71:I-239.

15.           Preston FW, Walsh WS, Clarke TH: Cutaneous neurofibromatosis (Van Recklinghausen’s disease); clinical manifestations and incidences of sarcoma in sixty-one patients. Arch Surg 1952;64: 813-27.

16.           Hankey GT. section of odontology. Von Recklinghausen's Disease with Local Tumour of the Palate. Proceedings of the Royal Society of Medicine. 1933;23-5.

17.           Miles DA, Wright BA. Palatal Swellings Associated with multilesional Disorders: Report of Cases. J Oral Maxillofac Surg 1986;44:666-8.

18.           Kumar CA, Jagat Reddy RC, Gupta S, Laller S. Oral hamartomas with von Recklinghausen disease. Ann Saudi Med 2011;31(4):428-30.

19.           Jouhilahti EM, Visnapuu V, Soukka T, et al. Oral soft tissue alterations in patients with neurofibromatosis. Clin Oral Invest 2012;16:551–8.

20.           Bharath TS, Krishna YR, Nalabolu GR, Pasupuleti S, Surapaneni S, Ganta SB. Neurofibroma of the Palate. Case Reports in Dentistry 2014;1-4.

21.           Campos MS, Fontes A, Marocchio LS, et al. Clinicopathologic and immunohisto-chemical features of oral Neurofibroma. Acta Odontol Scand 2012;70:577–82.

 

Corresponding Author

Dr.Chittemsetti Samatha,

Post Graduate Student,

Department of Oral Pathology,

Mamata Dental College,

Khammam, AP, India.

Ph: +91 9966952286,

Email: samathachittemsetti@gmail.com


 

 

 

Source of Support: Nil, Conflict of Interest: None Declared

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