[page 10] [Rare Tumors 2011; 3:e4]
Hassan Al Bisher,1Ravi Kant,1
Hospital of the University, Al Khobar,
Hospital of the University, Al Khobar,
of the submandibular gland
Ahmed Aldamati,1Aysha Ahmed Badar2
we report a case of plexiform neurofibroma in
a patient with a von Recklinghausen’s disease
(NF-1) who presented with a submandibular
mass mimicking a submandibular gland
tumor. Complete surgical excision provides the
best treatment and final diagnosis. A neurofi-
broma should be considered in the differential
diagnosis for submandibular mass.
in patient with von
1General Surgery Department, King Fahd
2Histopathology Department, King Fahd
Plexiform neurofibroma of the submandibu-
lar gland is an extremely rare tumor. Herein,
ple nervous fascicles.1Neurofibromas may
occur as part of the syndrome of neurofibro-
matosis (commonest), solitary neurofibromas,
or multiple neurofibromas without von
Recklinghausen’s disease (NF-1).2,3The plexi-
form neurofibromas of the submandibular
gland are extremely rare.4-8To date only five
cases had been reported in the literature
(Table 1) and only one case was not associated
with NF-1.5Herein, we report a case of sub-
mandibular gland plexiform neurofibroma in a
patient with NF-1.
A 17-year-old male presented with painless
left submandibular mass of five years duration.
The mass became enlarged and painful two
Plexiform neurofibroma is a benign periph-
eral nerve sheath tumor that surrounds multi-
years prior to his presentation. He had no
other relevant symptoms. Both his twin and
father have NF-1. A physical examination
revealed a non-tender 4¥5 cm mass in the left
submandibular region, firm in consistency, not
attached to the skin and without hypoglossal or
lingual nerve involvement. On systemic exam-
ination showed, signs of NF-1, multiple cuta-
neous neurofibroma and cafè-au-lait spots
over the body (Figure 1A, 1B and 1C).9An
investigation of complete blood count and ery-
throcytes sedmentation rate (ESR) were with-
in normal limits. The ultrasound of the left
submandibular region showed submandibular
complex mass with heterogeneous echogenic-
ity ill defined border. The computer tomogra-
phy (CT) scan of the neck revealed heteroge-
neous mass in the left submandibular gland
(Figure 2). The MRI T2-weighted image with
contrast showed a mass with diffuse heteroge-
neous enhancement in the left submandibular
gland (Figure 3A and 3B). Fine needle aspira-
tion cytology showed some clusters of acininc
cells but no malignant cell. Preoperative diag-
nosis was benign submandibular gland tumor.
The left submandibular gland excision was
performed. The origin of this tumor was not
obvious at surgery, though the hypoglossal and
lingual nerves were intact. The tumor was
thought to have originated from the secreting
nerve. The patient had an uneventful postoper-
ative period. Gross examination revealed a lob-
ulated, convoluted firm in consistency lesion.
It was heterogeneous, glistening, graywhite
tumor. Histopathological examination showed
elongated, spindly cells with wavy nuclei and
normal glandular tissue at periphery (Figures
4A and 4B). Immunohistochernical studies
showed positive staining of anti-S100 protein
(Figure 4C), bordered by faintly epithelial
membrane antigen (EMA). Six months follow
up after the left submandibular gland excision
was satisfactory with no local recurrence.
eral nerve (i.e. axons, Schwann cells and
fibroblasts).10,11Several forms had been
The neurofibroma is a benign tumor of neu-
ral origin comprise all elements of the periph-
Rare Tumors 2011; volume 3:e4
Correspondence: Hassan Al Bisher, General
Surgery Department, King Fahd Hospital of the
University, Al Khobar, eastern province, Saudi
Arabia. E-mail: email@example.com
Key words: submandibular gland tumor, plexi-
form neurofibroma, neurofibroma, Von Reckling -
Acknowledgement: we wish to express our thanks
to Dr Amani Mohammed for her contribution and
participation in the preparation of the manu-
Conflict of interest: the authors report no con-
flicts of interest.
Received for publication: 2 December 2010.
Revision received: 22 December 2010.
Accepted for publication: 23 December 2010.
This work is licensed under a Creative Commons
Attribution 3.0 License (by-nc 3.0).
©Copyright H. Al Bisher et al., 2011
Licensee PAGEPress, Italy
Rare Tumors 2011; 3:e4
Table 1. Literature review of submandibular gland plexiform neurofibroma.
Authors Sex AgeGland Origin FNANF1
Tsutsumi T5 1996
Bourgeois JM72001 M
Our case 2010
NA, Not available; -ve, negative; +ve: positive; Y, year; FNA, fine needle aspiration cytology; NF1, von Recklinghausen’s disease.
3 y Submandibular and parotid
29 y Submandibular
17 y Submandibular
Not diagnostic -VE
Not diagnostic +VE
Not diagnostic +VE
Not diagnostic -VE
Figure 1. Photograph showed left ankle cuta-
neous neurofibroma (A), right forearm cuta-
neous neurofibroma (B), and Cafè -au-lait
spots found on the body of the patient (C).
[Rare Tumors 2011; 3:e4][page 11]
described: cutaneous neurofibromas (both
localized and diffuse types), intraneural neu-
rofibromas (localized and plexiform), massive
soft-tissue neurofibromas (diffuse and plexi-
form), and visceral neurofibromas (solitary or
multiple) and sporadic or associated with NF-
1.12,13Plexiform neurofibromas are slow grow-
ing, painless and locally infiltrative tumors.14
Although plexiform neurofibromas appear as
benign, they have a 2-5% potential for malig-
nant transformation.15,16Most frequently occur
as a component of neurofibromatosis, though
they can also occur isolated without any neu-
rofibromatosis symptoms but they are
extremely rare.17,18Mostly occur in the head and
neck region because this area is richly inner-
vated.19They are uncommon tumors of the sali-
vary glands only 0.4% of salivary gland
tumors.20They represent 14% of all benign
mesenchymal tumors and 10% of non-epithe-
lial salivary gland tumors.20,21Most often had
been described in the parotid gland.8The diag-
nosis of submandibular gland plexiform neu-
rofibroma in all reported cases were based on
histopathological examination.4-8The diagnos-
tic yield of FNAC appears to be rather low.
Computer tomography scan and MR imaging of
plexiform neurofibroma may show multilobu-
lated masses that may appear as a bag of
worm.8The computer tomography imaging fea-
tures could be extremely helpful to the clini-
cian in appropriately advising the patients,
planning surgery and
Distinguishing between isolated neurofibroma
and those associated with NF-1 is important
because the treatment and prognosis different.
Neurofibromas associated with NF-1 are likely
to recur or undergo malignant transforma-
tion.10,22,23The current treatment of plexiform
neurofibroma involves surgery.22,24,25These
tumors are nonradiosensitive and limited ben-
efit had been observed with chemotherapy.26
The recurrence is seen in as many as 20% of
the patients with a plexiform neurofibroma
after complete resection and increases to 44%
with subtotal resection.8,27
gland. Although plexiform neurofibroma
tumors have a neurogenic rather than a sali-
vary gland origin, one must consider this kind
of tumors and it is essential to monitor
patients with NF-1 periodically for the possi-
bility of recurrence and malignant transfor-
We have reported an extremely rare case of
plexiform neurofibroma in submandibular
Recklinghausen: histórico, diagnósticos,
exames clínicos e laboratoriais. JBM
2. Neely JG. Neoplastic involvement of the
facial nerve. Otolaryngol Clin North Am
3. Batsakis JG. Tumors of the head and neck.
Clinical and pathological considerations.
2nd ed. Williams and Wilkins: Baltimore
4. Weitzner S. Plexiform neurofibroma of
major salivary glands in children. Oral
Surg Oral Med Oral Pathol 1980;50:53-7.
5. Tsutsumi T, Oku T, Komatsuzaki A.
Solitary plexiform neurofibroma of the
submandibular salivary gland. J Laryngol
6. Derekoy S, Sefali M. Plexiform neurofibro-
ma of the submandibular gland. J Laryngol
7. Bourgeois JM, Radhi J, Elden L, et al.
Plexiform neurofibroma of the sub-
mandibular salivary gland in a child. Can J
8. Aribandi M, Wood WE, Elston DM, et al. CT
features of plexiform neurofibroma of the
submandibular gland. AJNR Am J
9. National Institutes of Health Consesus
Development Conference Neurofibro -
matosis: Conference Statement. Arch.
1. Geller M, Bonalumi AF, França FC, et al.
Neurofibromatose. Síndrome de Von
Figure 2. Axial contrast-enhanced computer
tomography view demonstrating the hetero-
geneous mass of the left submandibular gland.
Figure 3. The MRI T-2 weighted image with
contrast (A. Axial & B. Coronal view) showed
a mass with diffuse heterogeneous enhance-
ment in the left submandibular gland.
Figure 4. Photomicrograph of the plexi-
form neurofibroma, Histopathological
image of the plexiform neurofibroma
along with normal glandular tissue
(Hematoxylin-Eosin stain) (A) , Elongated,
spindly cells with
(Hematoxylin-Eosin stain) (B), Immuno -
positive staining for the S-100 protein (C).
[page 12] [Rare Tumors 2011; 3:e4] Download full-text
10. Weiss SW, Goldblum JR. Benign tumors of
the peripheral nerves. Enzinger and
Weiss's soft tissue tumors. 4th ed. St
Louis, Mo: Mosby 2001;1122-46
11. Rosai J. Rosai and Ackerman's Surgical
Pathology, 9th ed. St. Louis: Mosby; 2004.
12. Burger PC, Scheithauer BW, Vogel FS.
Surgical Pathology of the Nervous System
and Its Coverings. Philadelphia: Churchill
13. Tamer E, Yalcin B, Alli N. Multiple nodular
plexiform neurofibromas in a neurofibro-
matosis 1 family: a familial tendency? A
case report and review of the literature. Int
J Dermatol 2003;42:357-8.
14. Keel SB, Rosenberg AE. Soft tissue pathol-
ogy of the head and neck. In: Pilch BZ. ed.
Head and Neck Surgical pathology.
Philadelphia: Lippincott Williams and
15. Hope DG, Mulvihill JJ. Malignancy in neu-
rofibromatosis. Adv Neurol 1981;29:33-56.
16. Rapado F, Simo R, Small M. Neuro -
fibromatosis type 1 of the head and neck:
dilemmas in management. J Laryngol Otol
17. Lin V, Daniel S, Forte V. Is a plexiform
neuroWbromatosis type I? Laryngoscope
18. Fisher DA, Chu P, McCalmont T. Solitary
Plexiform neurofibroma is not pathogno-
monic of von Recklinghausen’s neurofi-
bromatosis: a report of a case. Int J
19. Cebesoy O, Tutar E, Isik M, Arpacioglu O. A
case of isolated giant plexiform neurofi-
broma involving all branches of the com-
mon peroneal nerve. Arch Orthop Trauma
20. Seifert G, Miehlke A, Haubrisj J, et al.
Disease of the salivary glands. In:
Pathology, diagnosis, treatment, facial
nerve surgery. New York: Georg Thieme
21. McDaniel RK. Benign mesenchymal neo-
plasms. In: Ellis GL, Auclair PL, Gnepp DR,
editors. Surgical pathology of the salivary
glands. Philadelphia: WB Saunders 1991;
22. Packer RJ, Gutmann DH, Rubenstein A, et
al. Plexiform neurofibromas in NF1:
toward biologic-based therapy. Neurology
23. Scheithauer BW, Woodruff JM, Erlandson
RA. Tumor of the peripheral nervous sys-
tem. Armed forces Institute of Pathology
24. Korf BR. Plexiform neurofibromas. Am J
Med Genet 1999;89:31-7.
25. Crawford AH, Schorry EK. Neurofibro -
matosis update. J Pediatr Orthop 2006;26:
26. DeBella K, Szudek J, Friedman JM. Use of
the National Institutes of Health criteria
for diagnosis of neurofibromatosis 1 in
children. Pediatrics 2000;105:608-14.
27. Needle MN, Cnaan A, Dattilo J, et al.
Prognostic signs in the surgical manage-
ment of plexiform neurofibroma: the
Children’s Hospital of Philadelphia experi-
ence, 1974-1994. J Pediat 1997;131:678-82.