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PhiliPPine Journal of otolaryngology-head and neck Surgery 49
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Olfactory neuroblastomas (esthesioneuroblastomas, ONB) are rare malignant neoplasms
that arise from sensory neuroepithelial (neuroectodermal) olfactory cells found in the superior
nasal concha and the cribriform plate of the ethmoid sinus. ONBs comprise approximately 5% of
sinonasal tract malignancies, affect both genders equally and primarily involve the middle aged
adult group (range 3 – 79 years). The most common presenting symptoms are unilateral nasal
obstruction, epistaxis and a fairly slow-growing mass high in the nasal cavity or ethmoid region.
Anosmia is also characteristic. A classic, though advanced, radiologic presentation is that of a
“dumbbell-shaped” mass on either side of the cribriform plate, with an expansion into the nasal
vault and an opposite expansion into the intracranial cavity. 1, 2, 3
We present here two illustrative cases. The first is a 67-year-old male who has had three
recurrences of a left nasal mass over a span of 24 years. The initial occurrence was treated with
excision and radiotherapy while subsequent recurrences were treated with excision alone. The
material shown herein is from the latest recurrence. All previous slides were not available for
review. The second case is a 52-year-old male who presented with a six-month history of a right
nasal cavity mass that on initial consult already extended into the maxillary, ethmoid, sphenoid
and bilateral frontal sinuses, penetrated the cribriform sinus and involved the right frontal lobe of
the brain. A craniofacial resection was performed.
The typical case is best described as a “malignant small round cell tumor” arranged in rounded
lobules in a vascularized stroma (Figure1). This general architecture is found irrespective of the
grade of the tumor. The cells are neuroendocrine in appearance with uniform small round nuclei
that have “salt-and-pepper” nuclear chromatin (Figure 2) and scanty cytoplasm. Tumors are graded
according to the Hyams’ grading system. Grades 1 – 2 tumors have nil to few mitoses, minimal
nuclear pleomorphism, absent necrosis and presence of Homer-Wright pseudorosettes (Figure 3),
while Grades 3 – 4 tumors have brisk mitoses, prominent nuclear pleomorphism, frequent necrosis
and predominance of Flexner-Wintersteiner true rosettes (Figures 4, 5). The first case is an example
of a Grade 2 ONB while the second shows a Grade 4 morphology. Immunohistochemistry typically
shows diffuse positivity for the neuroendocrine markers neuron-specific enolase, chromogranin
and synaptophysin (Figure 6), and negative reactions for cytokeratins, desmin and CD99. The latter
three stains are significant in that the differential diagnoses include Sinonasal Undifferentiated
Carcinomas (SNUC), Rhabdomyosarcomas and Primitive Neuroectodermal Tumors/Ewing
Sarcomas (PNET/ES) in which these stains are expected to be positive, respectively.1, 3, 4 Other
differential diagnosis include a Non-Hodgkin Lymphoma and a Mucosal Malignant Melanoma for
which a Leukocyte Common Antigen (LCA) and melanoma markers (e.g. HMB-45 or Melan-A) may
be performed. The two cases were however sufficiently distinct as to rule out these two entities
on morphologic grounds.
Olfactory Neuroblastoma
Correspondence: Jose M. Carnate, Jr.,MD
Department of Pathology
College of Medicine
University of the Philippines Manila
547 Pedro Gil St., Ermita, Manila 1000
Philippines
Phone: (632) 526 4550
Fax: (632) 400 3638
Email: jmcjpath@yahoo.com
Reprints will not be available from the author.
The author declared that this represents original material
that is not being considered for publication or has not been
published or accepted for publication elsewhere, in full or in
part, in print or electronic media; that the manuscript has been
read and approved by the author, that the requirements for
authorship have been met by the author, and that the author
believes that the manuscript represents honest work.
Disclosures: The author signed a disclosure that there are no
financial or other (including personal) relationships, intellectual
passion, political or religious beliefs, and institutional affiliations
that might lead to a conflict of interest. Philipp J Otolaryngol Head Neck Surg 2010; 25 (2): 49-51 c Philippine Society of Otolaryngology – Head and Neck Surgery, Inc.
Jose M. Carnate, Jr.,MD
Department of Pathology
College of Medicine
University of the Philippines Manila
PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 25 no. 2 July – december 2010
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50 PhiliPPine Journal of otolaryngology-head and neck Surgery
Prognosis is stage - (90% 5-year survival rate for early-stage versus
40% for advanced-stage cases) and grade-dependent (80% for low-grade
versus 40% for high-grade cases). Recurrence occurs in approximately
30% of cases usually within two years. The long-term recurrences seen in
the first case is compatible with its low-grade morphology. In contrast,
the shorter history and high stage (Kadish stage C)4 at presentation of
the second case are both compatible with its high-grade morphology.
Metastases develop in about 20% of cases and usually involve the
lymph nodes, lungs and bone. Complete surgical excision with post-
operative radiotherapy is the mainstay of treatment. 1,2
Figure 1. Case 2 - Rounded lobules of cohesive tumor cells separated by a vascularized stroma
(Hematoxylin-Eosin, 40X).
(Hematoxylin-Eosin, 40X).
Figure 2. Case 1 - Uniform round nuclei with finely granular “salt-and-pepper” chromatin (Hematoxylin-
Eosin, 400X)
(Hematoxylin-Eosin, 400X)
Figure 3. Case 1 - Homer-Wright pseudorosette: tumor cells surround a pseudolumen that contains
neurofibrillary material (Hematoxylin-Eosin, 400X)
(Hematoxylin-Eosin, 400X)
Figure 4. Case 2 - Flexner-Wintersteiner true rosette: tumor cells surround a true central lumen
simulating a gland; note the nuclear pleomorphism (Hematoxylin-Eosin, 400X)
(Hematoxylin-Eosin, 400X)
PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 25 no. 2 July – december 2010
PhiliPPine Journal of otolaryngology-head and neck Surgery 51
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ACKNOWLEDGMENT
The author would like to acknowledge Drs. Ramon Antonio B. Lopa and Arsenio Claro A. Cabuncal
for the two cases and Drs. Treah May D. Suacillo and David Brian U. Olveda for the assistance in the
pathologic sign-out and preparation of the microscopic images.
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Figure 5. Case 2 - Nuclei that have more atypia and mitoses (Hemtaoxylin-Eosin, 400X)
(Hemtaoxylin-Eosin, 400X)
Figure 6. Archive case - Positive cytoplasmic reaction (Neuron-specific Enolase, 100X)
(Neuron-specific Enolase, 100X)