Nonneoplastic Lesions of the Nasal Cavity, Paranasal Sinuses, and Nasopharynx

Nonneoplastic Lesions of the Nasal Cavity, Paranasal Sinuses, and Nasopharynx

Most samples from the nasal cavity, paranasal sinuses, and nasopharynx are for nonneoplastic disease. Perhaps because they are so often routine (e.g., chronic sinusitis and inflammatory polyps), they may sometimes receive somewhat cursory histologic examination. That said, a variety of challenging nonneoplastic lesions occur within this region. Furthermore, the accessibility of the nasal cavity allows for biopsy and evaluation of some systemic diseases.

As with most nonneoplastic histologies, the pathologic findings are often nonspecific. The pathologist thus needs to be especially aware of clinical information in such cases. Indeed, both the clinician and pathologist may need to work together in such cases as both may be presented with nonspecific findings. With midline destructive lesions, the clinician’s differential may be vast, and treatment options may vary greatly depending upon the pathologist’s interpretation (Table 13.1).1,2 When confronted with granulomatous inflammation, the pathologist’s differential diagnosis may include infectious, autoimmune, iatrogenic, and even neoplastic conditions (Table 13.2).3,4 If the pathologist is to interpret such cases correctly, he will need to be fully armed with clinical and laboratory data. Even in such cases, he may, nonetheless, be sometimes forced to give more descriptive and qualified diagnoses.


Acute sinusitis is common following upper respiratory tract infection and is often due to infection by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. It is generally treated with antibiotics and is rarely sampled. If sampled, sinus tissue will show abundant edema and infiltration by a mixture of inflammatory cells with the predominant cell type being neutrophils.

Chronic sinusitis, on the other hand, is often sampled, as debridement is sometimes the surgical treatment of choice. The etiology of the disease is thought to be related to multiple factors including infection, allergy, and the individual patient’s anatomy and physiology.

TABLE 13.1 Midline Destructive Lesions



Acid-fast bacilli (tuberculosis and leprosy)

Rhinoscleroma (Klebsiella rhinoscleromatis)


Fulminant acute invasive fungal infection

Chronic invasive fungal infection


Other infections (spirochetes, parasites, etc.)


Wegener granulomatosis

Allergic granulomatosis and angiitis (Churg-Straus disease)

Other (systemic lupus erythematosis, polyarteritis nodosa, etc.)


Cocaine abuse


Neoplasia (especially NK/T-cell lymphoma)

NK cell, natural killer cell.

TABLE 13.2 Granulomatous Inflammatory Lesions

Infectious disease

Mycobacterium tuberculosis or leprosy (rarely other mycobacteria)

Fungal infection




Wegener granulomatosis

Allergic granulomatosis and angiitis (Churg-Straus disease)





FIGURE 13.1 Chronic sinusitis with stromal edema and chronic inflammation.

Histologically, the respiratory tissue will show variable inflammation composed mostly of lymphocytes, plasma cells, and eosinophils with the relative proportions of these cells to one another varying from case to case (Fig. 13.1, eFig. 13.1).5 Subepithelial and stromal fibrosis can be present depending on the overall chronicity of the process with epithelial hyperplasia and even polyp formation. Goblet cells may be more numerous, as may seromucinous glands. Fragments of underlying bone can have sclerotic, reactive changes.


A specific cause of chronic sinusitis is primary ciliary dyskinesia, also known as Kartagener syndrome. This disease is also associated with male sterility, chronic bronchitis, bronchiectasis, and situs inversus.6,7 It is a genetically heterogeneous disease and typically inherited in an autosomal recessive pattern. Diagnosis requires clinical findings with anatomic and/or genetic findings, as neither anatomic nor genetic testing is entirely sensitive and specific.8

From the anatomic pathologic standpoint, assessment for this disease is usually twofold. Functional analysis of the cilia typically involves a wet preparation of scraped nasal epithelium with assessment of the cilia motility. Normal function should be coordinated and demonstrate both intracellular and intercellular synchrony, with cilia typically beating at a frequency of 8 to 20 Hz. Normal function excludes a diagnosis of primary ciliary dyskinesia for all practical purposes. Anatomic analysis of the cilia
is performed by electron microscopy. Normal motile cilia are composed of microtubules arranged in a 9 + 2 configuration (Fig. 13.2). Each of the nine outer doublets is attached to the adjacent doublets via nexin links, contains both inner and outer dynein arms, and has radial spokes. A description of all the variants of dysmotile cilia is beyond this book; however, the majority of dysfunction is associated with the absence of inner and/or outer dynein arms.

FIGURE 13.2 Electron microscopy of normal cilia showing the classic 9 + 2 microtubule configuration. Outer (white arrow) and inner (black arrow) dynein arms are seen.


Fungi are the etiologic agents of a number of pathologies of the nasal cavities.9,10 Commonly, they are related to allergic rhinitis and thus may play some role in the development of chronic sinusitis and secondary complications from such. They also play a role in a number of other sinus pathologies that can be either noninvasive or invasive.

Allergic Fungal Sinusitis

Allergic fungal sinusitis is the most common fungal disease of the sinuses. Clinically, patients with this disease are immunocompetent and may have concomitant asthma, allergic rhinitis, and nasal polyps.11,12,13 The disease is suspected after a protracted history of sinusitis that has been refractory to treatments for bacterial sinusitis. It may be secondary to either hyaline molds such as Aspergillus or Fusarium species or to various dematiaceous molds.11,12,13,14

FIGURE 13.3 Mucus with numerous entrapped eosinophils.

Surgically collected specimens will grossly have tan-brown fragments of mucosa with green-brown mucoid material and have evoked for some the culinary impressions of cottage cheese and peanut butter.9 Histologically, samples show abundant mucus with entrapped eosinophils and Charcot-Leyden crystals (allergic mucus) (Fig. 13.3, eFig. 13.2).11,13 Although the fungal forms may be difficult to visualize with routine hematoxylin and eosin (H&E)-stained material, silver staining will show numerous hyphal fragments (Fig. 13.4, eFig. 13.3). The hyphal fragments often branch at 45-degree angles and may have occasional conidia.13 Fragments of edematous and inflamed respiratory mucosa will also be present, showing changes consistent with chronic sinusitis, and should not contain organisms when viewed with special stains.

Sinus Mycetoma (Fungus Ball)

Sinus mycetomas most often occur in the maxillary sinuses of immunocompetent patients.9,15 Patients may present with headache, facial pain, nasal obstruction, or a perceived nasty odor, and patients may even present with new-onset seizure and may sometimes have concomitant nasal polyps and sinusitis. The disease is most often caused by Aspergillus fumigatus.

Removed material will appear mucopurulent or cheesy.9 On sections, a dense collection of fungal elements will be seen, devoid of allergic mucus (Fig. 13.5). Silver staining is rarely needed due to the abundance of the fungus (eFig. 13.4). The fragments of sinus tissue will show changes of chronic sinusitis, and fungi should not involve fragments of respiratory mucosa.

FIGURE 13.4 A silver stain shows occasional hyphal fragments.

Invasive Fungal Sinusitis

Invasive fungal sinusitis is a disease generally restricted to immunocompromised individuals, although rare instances are noted in which the disease has affected immunocompetent persons.9,15,16,17,18 Acute or fulminant invasive fungal sinusitis may present as a painless, black, nasal septal, or palatal
eschar. It is most often caused by fungi of the order Mucorales such as Rhizopus and Mucor but may also be caused by Aspergillus and Fusarium species as well as dematiaceous species.

FIGURE 13.5 A fragment of a fungal ball.

FIGURE 13.6 Invasive fungi seen with silver stain.

Histologically, samples from patients with acute fungal sinusitis will show invasion of tissue by the hyphal elements often with involvement of vascular structures (Fig. 13.6, eFig. 13.5).9,10,16 A secondary vasculitis and thrombosis with resultant hemorrhage and infarction may also be seen. Surrounding inflammation is often minimal, a reflection of the immunocompromised state of the patient. Some have suggested the use of in situ hybridization for the typing of the etiologic agents.19

Chronic invasive fungal sinusitis follows a more protracted course than acute invasive fungal sinusitis.9,10 Patients are immunocompromised usually secondary to diabetes mellitus or previous treatment with corticosteroids. The disease may be associated with decreased vision and ocular immovability (orbital apex syndrome). Some believe the lesion begins as a sinus mycetoma that eventually becomes invasive due to the immunocompromised state of the patient. The disease is most often secondary to infection by A. fumigatus. As with acute invasive sinusitis, histologic sections show tissue and vascular invasion by hyphal elements, often with a limited inflammatory response.

Finally, paranasal granuloma or granulomatous invasive fungal sinusitis is a rare chronic fungal disease of immunocompetent patients that is associated with proptosis.9 The disease is secondary to infection by Aspergillus flavus. Most reports of this lesion come from Sudan.

Histologically, tissue invasion is present which induces nonnecrotizing granulomatous inflammation with intermixed plasma cells. At the centers of these granulomata, a small amount of fibrinoid necrosis with eosinophils may be present. An associated vasculitis may also be seen.


Involvement of the upper airway in tuberculosis is uncommon, and because of current chemotherapy, it is seldom considered in the differential diagnosis of nasal or pharyngeal disease.20,21 Infection with Mycobacterium tuberculosis can be primary to the site or secondary to a more widespread infection. Infection creates chronic symptoms with mucorrhea and epistaxis when the nasal cavity is involved, and cervical adenopathy is often noted with involvement of the nasopharynx. A discrete mass or ulcer may be present, and some ulcers may be deep enough to lead to perforation of the nasal septum. Histologically, sections will show caseating granulomata with Langhans-type giant cells (Fig. 13.7). Special staining for acid-fast bacilli may reveal organisms. Culturing the lesion is essential for the specific diagnosis.


Leprosy is an infectious, granulomatous disease that involves the skin and peripheral nerves and may sometimes involve the mucous membranes and nose.22,23 This is especially true with lepromatous leprosy.
It most often involves the inferior turbinates and septum, and crusting, obstruction, and bleeding may be noted. The typical histologic features of leprosy with epithelioid granulomata with foam cells are usually not seen with nasal samples. Investigators have noted that sections predominately show an inflammatory infiltrate rich in macrophages with admixed neutrophils, eosinophils, plasma cells, and mast cells (Fig. 13.8). Bacilli are easily identified with special stains and tend to be located within macrophages although nearly all cells may contain the organisms (eFig. 13.6).

FIGURE 13.7 Necrotizing granulomatous inflammation seen with tuberculosis.

FIGURE 13.8 Mixed inflammation with numerous macrophages seen with leprosy.


Rhinoscleroma is a chronic, granulomatous inflammatory condition caused by infection with Klebsiella rhinoscleromatis.24,25,26,27 It is endemic to Africa, Central and South America, South Central and Eastern Europe, the Middle East, and China. Sporadic cases, however, have been seen elsewhere, including in the United States.27 The disease almost always involves the nasal cavity, although it may extend into the palate or pharynx. It is not very contagious and affects primarily immunocompetent individuals.

Clinically, patients tend to be young, in their second or third decade of life, and may present with a midfacial necrotizing lesion. Patients may also initially notice a fetid, purulent rhinorrhea with nasal obstruction, and crusting, epistaxis, and nasal deformity can occur as the disease progresses (which can happen as early diagnosis is often missed).

The histology is characterized by the particular stage—exudative, proliferative, or fibrotic (cicatricial). The early exudative phase is characterized by abundant acute and chronic inflammation with suppurative necrosis or microabscess formation. Edema and granulation tissue may be present. The proliferative or granulomatous phase shows persistent chronic inflammation with groups or even sheets of foamy macrophages (Fig. 13.9, eFig. 13.7). Plasma cells may become prominent and Russell bodies are often seen. Special staining will reveal numerous gram-negative coccobacilli consistent with K. rhinoscheromatis (eFig. 13.8). Overlying pseudoepitheliomatous hyperplasia may also be present. The sclerotic stage is characterized by dense sclerosis with diminished chronic inflammation. Macrophages with definitive organisms may be difficult or impossible to identify at this stage.


Rhinosporidiosis is endemic to South India and Sri Lanka and is caused by the fungus, Rhinosporidium seeberi.26,28 The disease usually involves the nasal cavity and is usually unilateral. Clinically, the nasal mucosa may appear polypoid, and the patient may present with obstruction, epistaxis, or rhinorrhea. The epithelium may show ulceration. Abundant acute and chronic inflammation is usually present with eosinophils and occasional giant cells. Sporangia are easily identified and are characterized by thick walls and measure from 10 to 200µm in diameter (Fig. 13.10, eFig. 13.9).

FIGURE 13.9 Sheets of foamy macrophages seen in a case of rhinoscleroma.

FIGURE 13.10 Numerous sporangia seen in a case of rhinosporidiosis. (Courtesy of Dr. Alan Rose, University of MN.)


Nasal involvement is not uncommon in patients with cutaneous leishmaniasis, and it can sometimes be seen alone.29,30 Other portions of the upper respiratory tract may also be involved. Lesions can appear polypoid or simply as ulcers. Biopsy typically shows epithelial ulceration. Lymphoid aggregates, plasma cells, and granulomata are typically present with multinucleated giant cells. Histiocytes containing Leishman-Donovan bodies are often seen.29

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Jan 24, 2021 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Nonneoplastic Lesions of the Nasal Cavity, Paranasal Sinuses, and Nasopharynx

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