Human
Olfactory Biopsy
The Influence of Age and Seog I. Paik, MD; Michael \s=b\ Thirty-six mucosal
N.
Lehman, PhD; Allen M. Seiden, MD; Heather J. Duncan, PhD; David
specimens were obtained with a biopsy
instrument from the upper nasal septum of 12 human autopsy cases before the en bloc removal of the entire olfactory area. Examination ofthese 36 specimens with transmission electron microscopy demonstrated olfactory epithelium in only 17. A significant negative correlation (r=\m=-\.728) was noted between the age of the subject and the probability of obtaining olfactory epithelium, supporting the idea that the olfactory mucosa is gradually replaced by respiratory epithelium with aging. Using the en bloc specimens, the distribution of olfactory epithelium was reconstructed from light microscopic examination of silver-stained sections. Multiple patches of respiratory epithelium were observed over the upper portion of the nasal septum and superior turbinates, ie, the presumptive olfactory area. On transmission electron microscopic examination, fre-
quent respiratory metaplasia was also suggested. Within the
of respiratory metaplasia, supporting cell-like and microvillar cell-like structures often were found; these structures may be remnants of olfactory epithelium. The sampling of olfactory tissue with a biopsy procedure is hampered by the irregular and patchy distribution of olfactory epithelium. The invasion of respiratory epithelial patches into the olfactory mucosa seems to be characteristic of the human olfactory epithelium and may increase as a function of age. Thus, conclusions about the structure of the olfactory mucosa in an individual patient must be based on several tissue samples. (Arch Otolaryngol Head Neck Surg. 1992;118:731-738) area
the appears be considerable There and distribution of the human peripheral olfactory sys¬ be distributed The to
tem.
variation in
olfactory mucosa is thought to
structure across
the upper 10 mm of the nasal septum, beneath the cribriform plate, and over the medial wall of the superior turbinate.1 Al¬ though the olfactory epithelium in the human fetus has been reported to be uniform with distinct boundaries, the epithe¬ lium of adults may be characterized by irregular boundaries and interspersed patches of respiratory epithelium.2"4 These variations in the structure of the olfactory mucosa may be due to frequent infectious diseases of the nose, exposure to toxic chemicals, or head trauma, or may be an age-related
phenomenon.2,4-5
Ultrastructural studies of the olfactory mucosa have been conducted on a variety of vertebrate species, including var¬ ious mammals,6"17 birds,18 amphibia,19"21 and fish.22"24 Most of
Accepted
Receptor Distribution
publication December 17, 1991. From the Departments of Otolaryngology\p=n-\Headand Neck Surgery (Drs Paik, Seiden, Duncan, and Smith) and Anatomy and Cell Biology for
(Dr Lehman), University of Cincinnati (Ohio) Medical Center. Poster exhibit at the Annual Meeting of the American Academy of Otolaryngology\p=n-\Headand Neck Surgery, San Diego, Calif, September 9-13, 1990. Reprint requests to Department of Otolaryngology\p=n-\Headand Neck Maxillofacial Surgery, University of Cincinnati Medical Center, 231 Bethesda Ave, Cincinnati, OH 45267-0528 (Dr Smith).
V.
Smith, PhD
these studies agree that there are three classic cell types in the
olfactory epithelium: olfactory receptor cells, supporting (or
sustentacular) cells, and basal cells. Two different types of olfactory basal cells have been described in the mouse12: a dark basal cell (or basal cell proper) and a light (or globose)
basal cell. A fourth cell type was described in the dog that was postulated to be a precursor of the supporting cell.15 In addition, structural subclasses of receptor cells have been proposed in fish.22"24 Since the first ultrastructural observations on human ol¬ factory mucosa by Bloom and Engström,25 a number of mor¬ phologic studies of human autopsy material have been published.2'4-5-26"28 Biopsy samples of the olfactory epithelium were first obtained from living humans using a long, thin pair of toothed dissecting forceps.29 However, with the de¬ velopment of a specially designed biopsy instrument for ol¬ factory mucosa,30 a number of recent investigations have fo¬ cused on ultrastructural studies of olfactory epithelium in normal persons31,32 and in patients with olfactory dysfunction.33"37 Using this biopsy instrument, a fourth cell type, the microvillar cell, was first observed in the human olfactory epithelium by Moran et al.38 The role of these cells is unknown, but they may function as chemoreceptors.39 In addition to these ultrastructural studies, biopsy material from the human olfactory epithelium has been examined in normal persons and those with olfactory dysfunction using immunohistochemical methods.40"42 One of the problems with any biopsy procedure for the olfactory mucosa is the difficulty in reliably obtaining ol¬ factory epithelium in each tissue sample. For example, a recent study of patients with postviral olfactory dysfunc¬ tion found olfactory epithelium in only eight of 13 pa¬ tients.35 This poor success rate may reflect the irregular and patchy distribution of the human olfactory mucosa.2"4 Therefore, the purpose of the present study was to exam¬ ine the potential sampling error in this procedure. The bi¬ opsy instrument30 was used to collect tissue samples from fresh autopsy cases, from which the entire olfactory region was then removed for histologie examination. The distri¬ bution of olfactory and respiratory epithelium in the pre¬ sumptive olfactory mucosal region was evaluated at the light microscopic (LM) and ultrastructural levels.
SUBJECTS AND METHODS
Procedures for
Obtaining Specimens
mucosa within 24 hours specimens after death from 12 autopsy cases, aged between 34 and 85 years (Table). A careful review of medical history was done to rule out the most common causes of smell disorders. None of these cases had any known history of chronic nasal or sinus disease, head trauma, or recent upper respiratory tract infection. First, in each case, three samples (hereinafter referred to as biopsy samples) were obtained for transmission electron microscopic (TEM) examination from the uppermost part of the left nasal septum us¬ ing a biopsy instrument designed by Lovell et al,30 duplicating the
We collected
Downloaded From: http://archotol.jamanetwork.com/ by a Western University User on 06/07/2015
of the nasal
Characteristics of Autopsy Cases Case
No./
Age, y/Sex 1/34/M 2/39/F 3/51/M 4/56/M 5/5 7/M
Time After Death, h
Olfactory Samples/ TEM Samples*
18
3/3 2/3 2/3 2/3 1/3 1/3 1/3 1/3 2/3 0/3 1/3 1/3 17/36
16 23 22 20
6/58/M
6
7/63/M
17
8/65/M
19
9/69/F 10/76/M 11/82/F 12/85/F
2 12
22 20
Total *Number of samples containing olfactory epithelium among the transmission electron microscopic (TEM) samples obtained from the up¬ permost portion of the nasal septum. Pearson Product-Moment Corre¬ lation Coefficient between age and number of olfactory samples, r=-.728(P
Olfactory Biopsy
The Influence of Age and Seog I. Paik, MD; Michael \s=b\ Thirty-six mucosal
N.
Lehman, PhD; Allen M. Seiden, MD; Heather J. Duncan, PhD; David
specimens were obtained with a biopsy
instrument from the upper nasal septum of 12 human autopsy cases before the en bloc removal of the entire olfactory area. Examination ofthese 36 specimens with transmission electron microscopy demonstrated olfactory epithelium in only 17. A significant negative correlation (r=\m=-\.728) was noted between the age of the subject and the probability of obtaining olfactory epithelium, supporting the idea that the olfactory mucosa is gradually replaced by respiratory epithelium with aging. Using the en bloc specimens, the distribution of olfactory epithelium was reconstructed from light microscopic examination of silver-stained sections. Multiple patches of respiratory epithelium were observed over the upper portion of the nasal septum and superior turbinates, ie, the presumptive olfactory area. On transmission electron microscopic examination, fre-
quent respiratory metaplasia was also suggested. Within the
of respiratory metaplasia, supporting cell-like and microvillar cell-like structures often were found; these structures may be remnants of olfactory epithelium. The sampling of olfactory tissue with a biopsy procedure is hampered by the irregular and patchy distribution of olfactory epithelium. The invasion of respiratory epithelial patches into the olfactory mucosa seems to be characteristic of the human olfactory epithelium and may increase as a function of age. Thus, conclusions about the structure of the olfactory mucosa in an individual patient must be based on several tissue samples. (Arch Otolaryngol Head Neck Surg. 1992;118:731-738) area
the appears be considerable There and distribution of the human peripheral olfactory sys¬ be distributed The to
tem.
variation in
olfactory mucosa is thought to
structure across
the upper 10 mm of the nasal septum, beneath the cribriform plate, and over the medial wall of the superior turbinate.1 Al¬ though the olfactory epithelium in the human fetus has been reported to be uniform with distinct boundaries, the epithe¬ lium of adults may be characterized by irregular boundaries and interspersed patches of respiratory epithelium.2"4 These variations in the structure of the olfactory mucosa may be due to frequent infectious diseases of the nose, exposure to toxic chemicals, or head trauma, or may be an age-related
phenomenon.2,4-5
Ultrastructural studies of the olfactory mucosa have been conducted on a variety of vertebrate species, including var¬ ious mammals,6"17 birds,18 amphibia,19"21 and fish.22"24 Most of
Accepted
Receptor Distribution
publication December 17, 1991. From the Departments of Otolaryngology\p=n-\Headand Neck Surgery (Drs Paik, Seiden, Duncan, and Smith) and Anatomy and Cell Biology for
(Dr Lehman), University of Cincinnati (Ohio) Medical Center. Poster exhibit at the Annual Meeting of the American Academy of Otolaryngology\p=n-\Headand Neck Surgery, San Diego, Calif, September 9-13, 1990. Reprint requests to Department of Otolaryngology\p=n-\Headand Neck Maxillofacial Surgery, University of Cincinnati Medical Center, 231 Bethesda Ave, Cincinnati, OH 45267-0528 (Dr Smith).
V.
Smith, PhD
these studies agree that there are three classic cell types in the
olfactory epithelium: olfactory receptor cells, supporting (or
sustentacular) cells, and basal cells. Two different types of olfactory basal cells have been described in the mouse12: a dark basal cell (or basal cell proper) and a light (or globose)
basal cell. A fourth cell type was described in the dog that was postulated to be a precursor of the supporting cell.15 In addition, structural subclasses of receptor cells have been proposed in fish.22"24 Since the first ultrastructural observations on human ol¬ factory mucosa by Bloom and Engström,25 a number of mor¬ phologic studies of human autopsy material have been published.2'4-5-26"28 Biopsy samples of the olfactory epithelium were first obtained from living humans using a long, thin pair of toothed dissecting forceps.29 However, with the de¬ velopment of a specially designed biopsy instrument for ol¬ factory mucosa,30 a number of recent investigations have fo¬ cused on ultrastructural studies of olfactory epithelium in normal persons31,32 and in patients with olfactory dysfunction.33"37 Using this biopsy instrument, a fourth cell type, the microvillar cell, was first observed in the human olfactory epithelium by Moran et al.38 The role of these cells is unknown, but they may function as chemoreceptors.39 In addition to these ultrastructural studies, biopsy material from the human olfactory epithelium has been examined in normal persons and those with olfactory dysfunction using immunohistochemical methods.40"42 One of the problems with any biopsy procedure for the olfactory mucosa is the difficulty in reliably obtaining ol¬ factory epithelium in each tissue sample. For example, a recent study of patients with postviral olfactory dysfunc¬ tion found olfactory epithelium in only eight of 13 pa¬ tients.35 This poor success rate may reflect the irregular and patchy distribution of the human olfactory mucosa.2"4 Therefore, the purpose of the present study was to exam¬ ine the potential sampling error in this procedure. The bi¬ opsy instrument30 was used to collect tissue samples from fresh autopsy cases, from which the entire olfactory region was then removed for histologie examination. The distri¬ bution of olfactory and respiratory epithelium in the pre¬ sumptive olfactory mucosal region was evaluated at the light microscopic (LM) and ultrastructural levels.
SUBJECTS AND METHODS
Procedures for
Obtaining Specimens
mucosa within 24 hours specimens after death from 12 autopsy cases, aged between 34 and 85 years (Table). A careful review of medical history was done to rule out the most common causes of smell disorders. None of these cases had any known history of chronic nasal or sinus disease, head trauma, or recent upper respiratory tract infection. First, in each case, three samples (hereinafter referred to as biopsy samples) were obtained for transmission electron microscopic (TEM) examination from the uppermost part of the left nasal septum us¬ ing a biopsy instrument designed by Lovell et al,30 duplicating the
We collected
Downloaded From: http://archotol.jamanetwork.com/ by a Western University User on 06/07/2015
of the nasal
Characteristics of Autopsy Cases Case
No./
Age, y/Sex 1/34/M 2/39/F 3/51/M 4/56/M 5/5 7/M
Time After Death, h
Olfactory Samples/ TEM Samples*
18
3/3 2/3 2/3 2/3 1/3 1/3 1/3 1/3 2/3 0/3 1/3 1/3 17/36
16 23 22 20
6/58/M
6
7/63/M
17
8/65/M
19
9/69/F 10/76/M 11/82/F 12/85/F
2 12
22 20
Total *Number of samples containing olfactory epithelium among the transmission electron microscopic (TEM) samples obtained from the up¬ permost portion of the nasal septum. Pearson Product-Moment Corre¬ lation Coefficient between age and number of olfactory samples, r=-.728(P
