Abstract
There is considerable controversy in the diagnosis and classification of the type of inflammation that is attributed to various forms of chronic rhinosinusitis (CRS). Specimens obtained during surgical treatment of CRS have been invaluable resources for identifying the underlying inflammatory process. The classification of sinus inflammation is based on histopathologic examination of these surgical specimens. Accurate identification of the pathology and standardized reporting are invaluable for postsurgical treatment options and our understanding of CRS. In a large multispecialty referral hospital where multiple surgeons and pathologists are involved in clinical practice, the lack of standardization in specimen collection, specimen processing, and reporting introduce several variables that make it extremely difficult for retrospective analysis. This report focuses on consecutive endoscopic sinus surgical procedures performed by 4 different sinus surgeons over a period of 4 years in a Central Texas multispecialty hospital. This is an analysis of the reality of clinical practice without intervention. At the core of this analysis are pathology reporting practices for fungal sinus disease and the undesirable variables introduced by nonstandardized reporting. A practical classification of CRS based on pathology is proposed.
1
Introduction
Classification of chronic rhinosinusitis (CRS) has been an unresolved issue. There are several factors for the poor definition. As of 2012, we still do not have validated criteria to assess the presence and severity of sinusitis with confidence. Most symptoms used to categorize and classify sinus disease are not specific to the sinuses, reflecting the presence of nasal disease or lower respiratory tract disease. Even headaches and sinus pressure, the most commonly presumed associates of sinus disease, have not achieved relevance in our classification efforts because the sinuses do not seem to have pain sensory nerves. Similar limitations apply to imaging studies because comparing sinusitis symptom scores with computed tomographic (CT) scans to arrive at clinical relevance is not much better than random in predicting the presence or severity of CRS. Adding to the mentioned imperfections in our science, most research, analysis, and classification is conducted in academic tertiary centers, but most patients are treated by otolaryngologists in community hospitals, and results remain unreported and are not analyzed systematically. Many classification parameters used at academic centers are not part of clinical practice because of impracticality or inaccessibility to practitioners. Therefore, reports from academic centers may overestimate or underestimate distribution of disease. For any meaningful system of classification and calculations of prevalence and incidence, our research efforts need large standardized and comparable data sets. As the move to electronic health records gains momentum, usable research database can expand only if data acquisition through participation of community otolaryngologist and pathologists can be improved. To achieve this objective, a simpler, more feasible classification system based on objective parameters acquired through standardized methods using established practice patterns would have the easiest applicability and, therefore, the most impact. Such a system would use minimal subjective interpretation and rely in large part on histopathology. To demonstrate problems associated with data quality, this study includes a 4-year retrospective analysis of operative notes and surgical pathology reports of CRS submitted by 4 different surgeons and analyzed by 10 different pathologists. The focal point is selected as fungal sinus disease because this disease has relevant importance and high prevalence in the Southern United States . Accuracy in diagnostic analysis and reporting for CRS and fungal sinus disease is crucial in identifying nuances that may have implications for our poorly evidenced classification attempts.
2
Fungal sinus disease
There are recognized difficulties in accurately estimating the frequency of a causal relationship between fungi and rhinosinusitis because quality and availability of data depend on the various diagnostic criteria and laboratory techniques selected .
Allergic fungal sinusitis (AFS) was first described in 1981 as allergic aspergillosis by Millar et al and further defined by Katzenstein et al in 1983. Others have published clinical, laboratory, and histopathologic criteria to further define this newfound domain. Several authors deserve credit for the improvements on the diagnostic criteria. A collection of these contributions can be found and tracked in Schubert’s monograph . A liberal list of requirements for the diagnosis of AFS is presented below and includes entries that have been revised later. Because no consensus exists, all proposed criteria are presented regardless of the contradictory nature of entries, to draw attention to the complicated state of our diagnostic affairs. The list is as follows:
- 1.
Diagnosis of AFS is primarily histopathologic.
- 2.
Hematoxylin-eosin and Gomori methenamine-silver (GMS) stains of surgical pathology are required for the diagnosis.
- 3.
Presence of inhalant atopy needs documented (positive type I immediate hypersensitivity by in vitro or skin test to fungus recovered during surgery)
- 4.
Elevated serum total immunoglobulin E (IgE) is often present, needs documented.
- 5.
Allergic mucin must be observed at surgery or histopathologically.
- 6.
Allergic mucin must be positive for fungal staining or cultures.
- 7.
If allergic mucin is devoid of fungus, eosinophilic mucin rhinosinusitis is considered as diagnosis.
- 8.
IgE and IgG sensitivity and specificity for AFS are unknown, atopy is not seen in all patients, and the involvement of either type 1 or type 2 hypersensitivity reaction in AFS is speculative.
- 9.
Allergic mucin is not fungal debris.
- 10.
Allergic mucin refers to a histologic definition of the inflammatory cell type consisting of eosinophils and lymphocytes.
- 11.
Charcot-Leyden crystals are present independent from fungus presence.
- 12.
No fungal tissue invasion, mucosal necrosis, granulomas, or giant cells should be present.
- 13.
Polyps are present (ranges from “always” to “almost always” to “frequently” to “often”)
- 14.
Computed tomography scan findings consistent with CRS.
- 15.
Characteristic CT scan findings for fungal sinusitis (near-complete opacification and expansion, hyperattenuating allergic mucin) .
The multitude of the “correct” methods for the diagnosis of AFS sets the stage for an ever increasing number of interpretations. In clinical practice, these clinical, surgical, radiologic, immunologic, and histopathologic criteria are applied liberally in variable proportions. The resulting information and contribution from different studies at times fluctuates between incomparable to incompatible.
2
Fungal sinus disease
There are recognized difficulties in accurately estimating the frequency of a causal relationship between fungi and rhinosinusitis because quality and availability of data depend on the various diagnostic criteria and laboratory techniques selected .
Allergic fungal sinusitis (AFS) was first described in 1981 as allergic aspergillosis by Millar et al and further defined by Katzenstein et al in 1983. Others have published clinical, laboratory, and histopathologic criteria to further define this newfound domain. Several authors deserve credit for the improvements on the diagnostic criteria. A collection of these contributions can be found and tracked in Schubert’s monograph . A liberal list of requirements for the diagnosis of AFS is presented below and includes entries that have been revised later. Because no consensus exists, all proposed criteria are presented regardless of the contradictory nature of entries, to draw attention to the complicated state of our diagnostic affairs. The list is as follows:
- 1.
Diagnosis of AFS is primarily histopathologic.
- 2.
Hematoxylin-eosin and Gomori methenamine-silver (GMS) stains of surgical pathology are required for the diagnosis.
- 3.
Presence of inhalant atopy needs documented (positive type I immediate hypersensitivity by in vitro or skin test to fungus recovered during surgery)
- 4.
Elevated serum total immunoglobulin E (IgE) is often present, needs documented.
- 5.
Allergic mucin must be observed at surgery or histopathologically.
- 6.
Allergic mucin must be positive for fungal staining or cultures.
- 7.
If allergic mucin is devoid of fungus, eosinophilic mucin rhinosinusitis is considered as diagnosis.
- 8.
IgE and IgG sensitivity and specificity for AFS are unknown, atopy is not seen in all patients, and the involvement of either type 1 or type 2 hypersensitivity reaction in AFS is speculative.
- 9.
Allergic mucin is not fungal debris.
- 10.
Allergic mucin refers to a histologic definition of the inflammatory cell type consisting of eosinophils and lymphocytes.
- 11.
Charcot-Leyden crystals are present independent from fungus presence.
- 12.
No fungal tissue invasion, mucosal necrosis, granulomas, or giant cells should be present.
- 13.
Polyps are present (ranges from “always” to “almost always” to “frequently” to “often”)
- 14.
Computed tomography scan findings consistent with CRS.
- 15.
Characteristic CT scan findings for fungal sinusitis (near-complete opacification and expansion, hyperattenuating allergic mucin) .
The multitude of the “correct” methods for the diagnosis of AFS sets the stage for an ever increasing number of interpretations. In clinical practice, these clinical, surgical, radiologic, immunologic, and histopathologic criteria are applied liberally in variable proportions. The resulting information and contribution from different studies at times fluctuates between incomparable to incompatible.
3
Methods
Institutional review board approval for retrospective chart review at a large private tertiary referral hospital (Scott & White Memorial Hospital, Temple, TX) in Central Texas was obtained. Operative records of 4 senior sinus surgeons from January 1, 2007, to December 31, 2010, were reviewed. All sinus surgical procedures were listed. A total of 178 procedures were identified to have been performed for treatment of chronic sinus disease and/or polyps unresponsive to medical treatment. The definition of medical treatment responsiveness or indications for surgery were not investigated because this is outside of the scope or purpose of this study. Revisions and repeat surgeries on the same subject were excluded. Sinus procedures performed for access to the pituitary or for maxillofacial trauma are excluded. Sinus surgery performed for complications of acute sinusitis and to control infection in immunodeficient subjects were excluded. Balloon dilation–only procedures with no specimen sampling were excluded. Pathology reports were authored and signed by 10 different pathology attending physicians.
Among the 178 subjects, 4 had inverted papillomas and 1 had lymphoplasmocytoma. These were excluded. A total of 173 patients were included in the analysis. Pathology reports were used to obtain 4 separately identifiable groups based on key criteria below:
CRS group : Pathology diagnosis is chronic inflammation, lists neutrophils as the predominant inflammatory cell type, categorizes the inflammation as chronic sinusitis, or subacute sinusitis. Total of 98 subjects. Four had Charcot-Leyden crystals (CLCs).
Polyp group : CRS identifiers plus surgeons’ and pathologists’ identification and description of tissue as polyps (not polypoid changes). Total of 25 subjects; 3 with CLCs and 8 with antrochoanal polyps.
EOS (eosinophil) group : Pathology diagnosis is eosinophilic inflammation or chronic allergic sinusitis. Report describes eosinophils as the predominant inflammatory cell type, various descriptions of eosinophil presence (eosinophil abundance, eosinophilic abscess, eosinophilic infiltrates, allergic sinusitis) as described by the pathologist, with or without polyps as described by the surgeon. Charcot-Leyden crystals were present in all. Total of 16 subjects. Only 3 subjects had polyps.
Fungus group : Pathology report includes description of fungal elements such as hyphae, fungus, positive GMS staining, organisms morphologically consistent with fungus, or fungus ball. Charcot-Leyden crystals were present in 7; polyps, in 7; EOS, in 7. Total of 26 subjects. (One fungus ball was reported, involving the maxillary sinus and the ipsilateral ethmoid sinus; mucin was present.)
No invasive fungal sinus disease was reported.
Age and sex differences between groups were negligible.
Fig. 1 shows the percentage distribution based on pathology.
