2016, Volume 32, Number 3, Page(s) 196-199
Nasal Polyp – An Incidental Paraganglioma
Ruchi SRIVASTAVA1, Neelam WADHWA1, Shikha GUPTA2, Urvashi RAZDAN3
1Department of Pathology, University College of Medical Sciences, DELHI, INDIA
2Departments of Pathology, Jag Pravesh Chandra Hospital, DELHI, INDIA
3Departments of Otorhinolaryngology, Jag Pravesh Chandra Hospital, DELHI, INDIA
Keywords: Nose, Paraganglioma, Epistaxis, Extra-adrenal, Nasal polyp
The nose is an uncommon site for head and neck paraganglioma. The
diagnosis is seldom established pre-operatively; its rarity, infrequent
functionality and often benign biologic outcome underlie this fact.
We present one such case in a 60-year-old man who presented with
right nasal obstruction and episodic epistaxis. Rhinoscopy revealed
a fleshy polypoid mass arising from the anterior cartilaginous nasal
septum. Imaging studies excluded extra-nasal extension. The tumor
was highly vascular showing numerous variable sized, mostly thin
walled branching blood vessels akin to stag-horn shape simulating
a vascular neoplasm. There were large areas of hyalinization. The
typical tumor morphology was discernible only in focal areas.
Immuno-histochemistry confirmed the diagnosis. The tumor cells
expressed neuron specific enolase; S-100 stain demonstrated a vague
zell-ballen pattern. Paraganglioma is a rare histologic diagnosis in
nasal polypectomy specimen. We discuss the approach to exclude its
morphologic mimics including vascular tumors.
Tumors of paraganglia arising outside the adrenal medulla
are called paraganglioma (PG)1
. They may come to
clinical attention due to their potentially curable symptoms
associated with hyper-function. Although considered the
extra-adrenal counterpart of pheochromocytoma, they
differ from the latter in many aspects. The head and neck
(HN) region is the most common extra-adrenal site for
these tumors, however nasal location of such tumors is
. We share our experience with this unexpected
occurrence and discuss the diagnostic approach to exclude
its morphologic mimics.
A 60-year-old male presented to a tertiary care hospital in
Delhi with complaints of right nasal mass of 8-10 weeks
duration causing obstruction and intermittent epistaxis. There were no complaints of rhinorrhea, allergy, headache,
palpitation, tinnitus or cranial nerve palsies. He had
undergone an appendectomy 18 years ago. General physical
examination did not reveal any abnormalities of pulse or
blood pressure. Rhinoscopy revealed a fleshy, polypoid
mass arising from the anterior cartilaginous nasal septum
and distending the right nostril. It bled on touch during
the examination. Pre-operative investigations including
imaging studies were unremarkable. With a clinical
diagnosis of an inflammatory nasal polyp, right nasal
polypectomy was performed under general anesthesia. The
sessile polyp was excised along with an adjacent sleeve of
mucoperichondrium and anterior nasal packing done for
48 hrs. His intra-operative period and post-operative course
were uneventful. Subsequent radiologic investigations were
unremarkable. The patient had been asymptomatic in his
18 months follow up.
The specimen consisted of a single mucosa covered
polypoid soft tissue mass measuring 1.5 x 1.0 x 0.4 cm. It
was formalin fixed and paraffin embedded in toto. Sections
revealed a highly vascular well circumscribed tumor. The
vascular channels' caliber varied from small to ectatic; few
were branching and stag-horn shaped. Majority of vessels
were thin walled, few larger ones had thicker walls. There
were large intervening areas of hyalinization especially
prominent in the perivascular location (Figure 1). The
cellular areas were few and showed large cells arranged
in sheets and nests. The cells had abundant clear to pale
eosinophilic granular cytoplasm (Figure 2). Few showed
cytoplasmic vacuoles. Nuclei were centrally located and
contained inconspicuous nucleoli in many cells. Mitoses
were occasional; there were no areas of necrosis. The tumor
was reaching up-to the overlying epithelium, which showed
squamous metaplasia and focal ulceration. Although PG
was suspected, definite diagnosis was deferred to immunohistochemistry
(IHC). Polygonal cells with abundant pale
cytoplasm in a highly vascular hyalinized background
raised other possibilities- malignant melanoma, metastatic
carcinoma, PEComa, chordoma, glomus tumor and
epithelioid hemangioendothelioma (EH). The high
vascularity and hyalinization warranted exclusion of sinonasal
type hemangiopericytoma (SNTHP) and solitary
fibrous tumor (SFT).
Click Here to Zoom
|Figure 1: Numerous variably sized blood vessels with perivascular
hyalinization simulating a vascular neoplasm (H&E; x 200).
Click Here to Zoom
|Figure 2: High magnification of the cellular area highlighting
the voluminous clear to pale vacuolated cytoplasm in tumor cells
(H&E; x 400).
A panel of IHC comprising chromogranin A, neuron
specific enolase (NSE), S-100, HMB-45, CD34, CD31,
cytokeratin, epithelial membrane antigen (EMA), smooth
muscle antigen (SMA) and desmin was performed using
appropriate positive and negative controls. Tumor cells
strongly expressed chromogranin A and NSE (Figure 3).
S-100 expression was scarce and outlined the occasional sustentacular cells and zellballen pattern. CD31 and CD34
expression was limited to endothelial cells (Figure 4). Results
of other immuno-stains were negative/ non-contributory.
Hence the diagnosis of PG of nose was confirmed.
Click Here to Zoom
|Figure 3: Diffuse and strong NSE immuno-expression in tumor
cells (NSE; x200).
Click Here to Zoom
|Figure 4: CD34 immuno-stain is negative in tumor cells. The
endothelial cells acting as an internal control are positive (CD34;
PGs, the neural crest origin tumors arise from paraganglia,
structures lying adjacent to autonomic ganglia1
HN region is the most common site of PG followed by
abdominal and thoracic2
. Almost half of HN PGs are
located at carotid artery bifurcation. Others in descending
frequency in this region are jugulotympanic tumors and
. Rare sites of HN PG include nose,
orbit, larynx and thyroid1,3,4
. Almost all HN PGs
are suspected pre-operatively either due to their peculiar location and/or typical imaging characteristics. Only 1.2%
of HN PGs are true incidentilomas, i.e. require pathological
examination of an indeterminate mass to confirm the
diagnosis, as happened in our case2
HN PGs differ from abdominal PGs in many aspects2,3.
They are associated with parasympathetic nervous system,
while abdominal PGs show evidence of sympathetic
activity. Despite ultra-structural evidence of neuroendocrine
differentiation in HN PGs, less than 10%
produce catecholamines in amounts sufficient to result
in headaches, palpitations and perspiration. This is in
contrast to almost one-forth of abdominal PGs patients
having such symptoms. The frequency of hypertension in
HN PGs (42%) is also reported to be lower than abdominal
ones (64%)2. Endocrine silence of HN PGs usually
makes them symptomatic either as space occupying lesion
related to their anatomic site or with symptoms secondary
to nerve compression such as tinnitus and cranial nerve
palsies2,3. HN PGs are distinctly smaller and less likely
to be malignant than their abdominal counterparts2,5.
In a retrospective analysis, Flines et al. did not find any
difference in survival between their cohort (mean follow up
= 26.4 years) in comparison to the general population. The
deaths in their study population were attributed to surgical
complications of carotid body tumors5. Up-to 30% of HN
PGs may be associated with mutations of genes encoding
various subunits of succinyl dehydrogenase (SDH) enzyme.
Familial PGs are commonly multiple, bilateral and present
at an earlier age than sporadic tumors. Molecular tests are
indicated only in the setting of family history, previous
pheochromocytoma, multiple tumors and age < 40 years6.
The nose is an exceptional site of PG. Till date, less than 50
nasal PGs have been described, a testimony to its rarity (1,
3-5, 7-10). Nasal PGs have been reported in a wide age range,
8-72 years3,7. They often present with nasal obstruction
and/or epistaxis as happened in our case3,4,7. The
highly vascular nature of the tumor and trauma attendant
to its peculiar location may explain the epistaxis. It may
be said that most nasal PGs are non-functional, although
occasional reports of Cushing's syndrome secondary to
ACTH production are on record8. Distinction of de
novo nasal PGs arising from nasal mucosa from extension
of jugulo-tympanic or vagal tumors is essential to decide
surgical aspects and is based on radiologic features9. As
for HN PGs, most reported nasal tumors have had a benign
course, although occasional cases with late recurrence have
also been reported10.
The typical morphology of PGs composed of chief cells
and surrounding sustentacular cells may not be obvious in
all cases. Extensive secondary changes like hyalinization,
ectatic blood vessels, sclerosis and others may render
their recognition difficult as happened in our case. NSE
expression is almost invariable in PGs. The sustentacular
cell network is outlined by S-100 and GFAP immunostains.
Demonstration of sustentacular cells may be difficult
when tumor cells are present in sheets or large nests,
especially in small or fragmented sections1. Neither
atypical histological features nor infiltration are considered
indicative of malignancy. Metastasis to organs normally
devoid of chromaffin cells remains the only evidence of
Cellular areas of PGs may resemble malignant melanoma,
metastatic carcinoma, chordoma, perivascular epithelioid
cell tumor (PEComa), glomus tumor and EH, all tumors
rare to the nose11-17. They share cytologic feature of
voluminous clear to eosinophilic cytoplasm of the tumor
cells. Malignant melanomas usually have prominent
nucleoli; they invariably show diffuse positivity for S-100
and HMB-4511. Appropriate clinical setting and
expression of epithelial markers will help establishing
diagnosis of metastatic carcinoma12. Physalliferous cells
are characteristic of chordoma, but may be few. Chordomas
are decorated by cytokeratin, EMA and S-10013. In the
present case thorough search neither revealed cells with
prominent nucleoli nor with spidery cytoplasm. PGs do not
stain with epithelial markers or HMB-45 and S-100 staining
is limited to sustentacular cells. Radial arrangement of
cells around blood vessels and low grade nuclei are seen
in PEComa and glomus tumor. Although highly vascular,
our case showed large areas of perivascular hyalinization
rather than cellularity typical of these tumors. PEComas and glomus tumors typically stain with HMB-45 and SMA
respectively1,14,15. Expression of desmin is variable
in both. PGs are typically negative for HMB-45, SMA and
desmin. Conversely PEComas and glomus tumors do not
express NSE. EH, an angiocentric tumor may show clusters
of large cells resembling PG. Intra-cytoplasmic vacuoles
often containing erythrocytes indicate its vascular origin.
Endothelial cell markers like CD31 and CD34 are expressed
consistently in EH1,16. The cells in the present case did
have vacuolated appearing cytoplasm but did not have the
typical blistered look of EH; none contained erythrocytes.
IHC for CD31 and CD34 outlined the endothelial cells
lining the ecstatic vessels; tumor cells did not take the stain.
Highly vascular tumors with staghorn-like branching
vessels and prominent hyalinization in this region, albeit
rare include SNTHP and SFT17,18. SNTHP is a low to
intermediate grade tumor of perivascular myoid phenotype
containing HP like staghorn vessels. Its cells are bland,
spindle shaped and arranged in fascicular and/or whorled
pattern. Their immuno-phenotype resembles glomus
tumor rather than HP. Most react with vimentin (98%),
SMA (92%), and factor XIIIa (78%); expression of CD34 is
variable17. The cells in our lesion were polygonal rather
than spindle and their immuno-phenotype was typical of
neuro-endocrine nature. SFT, a fibroblastic mesenchymal
tumor also has prominent HP like branching vasculature. Its
cells are generally arranged in fascicular fashion unlike the
nesting pattern of polygonal cells of PGs. Its cells stain with
CD34, bcl-2 and CD9918. CD34 stain was consistently
absent in tumor cells in our case.
To conclude, we have shared our experience with an
unsuspected nasal PG. This rare neoplasm of the nose is
likely to be a histologic surprise in the rather common
nasal polypectomy specimens. Identification of its typical
morphology is essential for correct diagnosis and proper
management. Immuno-staining for NSE and chromogranin
A is likely to be useful in cases obscured by extensive
1) Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors.
5th ed. China: Mosby Elsevier; 2008.
2) Erickson D, Kudva YC, Ebersold MJ, Thompson GB, Grant CS,
van Heerden JA, Young WF Jr. Benign paragangliomas: Clinical
presentation and treatment outcomes in 236 Patients. J Clin
Endocrinol Metab. 2001;86:5210-6.
3) Lack EE, Cubilla AL, Woodruff JM, Farr HW. Paragangliomas of
the head and neck region: A clinical study of 69 patients. Cancer
4) Zainine R, Sahtout S, Ouertani H, Sellami M, Beltaief N, Besbes
G. Paraganglioma of the nasal cavity. Tunis Med. 2012;90:178-9.
5) de Flines J, Jansen J, Elders R, Siemers M, Vriends A, Hes F,
Bayley JP, van der Mey A, Corssmit E. Normal life expectancy
for paraganglioma patients: A 50-year-old cohort revisited. Skull
6) Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M,
Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe
K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S,
Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss
MM, Peczkowska M, Kubaszek A, Pigny P, Ward RL, Learoyd
D, Croxson M, Zabolotny D, Yaremchuk S, Draf W, Muresan
M, Lorenz RR, Knipping S, Strohm M, Dyckhoff G, Matthias
C, Reisch N, Preuss SF, Esser D, Walter MA, Kaftan H, Stöver T,
Fottner C, Gorgulla H, Malekpour M, Zarandy MM, Schipper J,
Brase C, Glien A, Kühnemund M, Koscielny S, Schwerdtfeger P,
Välimäki M, Szyfter W, Finckh U, Zerres K, Cascon A, Opocher
G, Ridder GJ, Januszewicz A, Suarez C, Eng C. Clinical predictors
for germline mutations in head and neck paraganglioma patients:
cost reduction strategy in genetic diagnostic process as fall-out.
Cancer Res. 2009;69:3650-6.
7) Ketabchi S, Massi D, Santoro R, Franchi A. Paraganglioma of
the nasal cavity: A case report: Eur Arch Otorhinolaryngol.
8) Lieberum B, Jaspers C, Münzenmaier R. ACTH-producing
paraganglioma of the paranasal sinuses. HNO. 2003;51:328-31.
9) Amiraraghi N, Syed MI, Syed S, Williams AT. Paraganglioma
of the skull base presenting as nasal polyps. Laryngoscope.
10) Sharma HS, Madhavan M, Othman NH, Muhamad M, Abdullah
JM. Malignant paraganglioma of frontoethmoidal region. Auris
Nasus Larynx. 1999;26:487-93.
11) Harvey RJ, DAlgorf DM. Chapter 10: Sinonasal malignancies.
Am J Rhinol Allergy. 2013;1:35-8.
12) Terada T. Renal cell carcinoma metastatic to the nasal cavity. Int J
Clin Exp Pathol. 2012;5:588-91.
13) Gupta N, Kaur J, Srinivasan R, Das A, Mohindra S, Rajwanshi
A, Nijhawan R. Fine needle aspiration cytology in lesions of the
nose, nasal cavity and paranasal sinuses. Acta Cytol. 2011;55:
14) Bandhlish A, Leon Barnes E, Rabban JT, McHugh JB. Perivascular
epithelioid cell tumors (PEComas) of the head and neck: Report
of three cases and review of the literature. Head Neck Pathol.
15) Daugaard S, Jensen ME, Fischer S. Glomus tumours. An
immunohistochemical study. APMIS 1990;98:983-90.
16) Requena L, Kutzner H. Hemangioendothelioma. Semin Diagn
17) Thompson LD, Miettinen M, Wenig BM. Sinonasaltype
hemangiopericytoma: A clinicopathologic and
immunophenotypic analysis of 104 cases showing perivascular
myoid differentiation. Am J Surg Pathol. 2003;27:737-49.
18) Vermeulen S, Ketels P, Salgado R, Creytens D, Vanderveken OM,
Claes J. Solitary fibrous tumour of the nasal cavity: A case report
and literature review. B-ENT. 2012;8:219-23.