Sunday, February 27, 2011

Theories of nasal polyposis




Introduction:

During the past century several theories have been proposed to explain the etiopathogenesis of nasal polyposis. The fact that so many theories have been proposed is the evidence of our poor knowledge of this topic. Majority of these theories are based on tissue oedema, increase in the number of tubulo-alveolar glands, presence of cysts of mucous glands.

Adenoma fibroma theory of Billroth:
Billroth in his studies found a large number of tubular glands in the nasal polypoidal tissue studied. He concluded that these glands were not normally seen in such large numbers in the nasal mucosa. He hence interpreted nasal polyp to be adenomas that began growing under the nasal mucosa pushing the epithelium and nasal glands outwards. However Hopmann disagreed with this hypothesis saying that the glandular tissue found in the tissue samples of nasal polypi studied contained only mucous glands normally found in the nasal mucosa and concluded that nasal polypi could be soft fibromas and used the term fibroma theory to explain this. These two theories are not currently accepted at present.













Figure showing increase in the number of nasal mucosal glands


















Figure showing development of nasal polypi due to increase in the number of nasal mucosal glands (Adenoma theory)

Necrotizing ethmoiditis theory of Woakes:
This theory suggests that ethmoiditis causes periostitis and ostitis of ethmoid bone causing bone necrosis. The necrotic bone initiates mucosal reaction leading on to mucosal oedema and polyp formation. This theory has been flawed from the very begining as no evidence of bone necrosis could be found in the polypoidal tissue studied so far.

Glandular cyst theory:

Evidently this theory is based on the presence of cystic glands and mucous filled cysts in the nasal polypoid tissue. The probable cause for the formation of these glandular cysts could be oedema of submucosa causing obstruction to the drainage of mucoid glands present in the nasal mucosa. These mucous cysts expands outwards pushing the nasal mucosa causing the polyp to occur. Taylor in his meticulous study has proved that mucous glandular cysts usually occur after the polyp has formed and hence he believed that glandular cysts could be caused by nasal polyposis and not vice versa.
Mucosal exudate theory of Hayek:
Hayek beleived that nasal polyp formed due to accumulation of exudate localised deep in the mucosa. This accumulation of exudate causes the mucosa to bulge leading to polyp formation. Nasal mucosal glands and tubuloalveolar glands are also
displaced outwards. These glands are hence found in the distal part of the polyp.
Theory of cystic dilatation due to obstruction of excretory ducts of nasal glands and blood vessel obstruction:








Figure showing cystic enlargement of nasal mucosal glands








Figure showing cyst formation prior to nasal polyposis

In chronic inflammation involving nasal mucosa blocks the excretory ducts of nasal tubulo alveolar glands causing the glands to dilate due to pent up secretions within. The blood vessels (capillaries and veins) surrounding these distending glands are also stretched. Stretching of these blood vessels impedes blood circulation and causes tissue oedema due to transudation of fluid. This theory is not valid due to the fact that dilatation of mucous glands occur only after formation of nasal polypoidal tissue.
Blockade theory of Jenkins:

This theory is based on the premise that development of nasal polypi is almost always preceded by certain degree of nasal mucosal inflammation. The inflammation could be the result of either infection / allergy. Histologically polyp itself is accumulation of intracellular fluid dammed up in a localized tissue. If this blockage persists polyp develop, if the blockage covers a large area then multiple polypi forms. This theory doesnt explain why nasal polyp prefers certain areas of nasal cavity.

Periphlebitis / perilymphangitis theory of Eggston and Wolff:
This theory is based on the premise that recurrent infections of nasal mucosa blocks intercellular fluid transport mechanism in the mucosa. This is always associated with oedema of lamina propria. This theory is based on the demonstration of chronic vascular changes in the nasal mucosa in response to inflammation. Histologically these changes are supposed to be rather diffuse and hence cannot be used to explain the pathogenesis of nasal polypi which can always be localised to certain areas of nasal cavity.

Glandular hyperplasia theory of Krajina:

According to Krajina chronic inflammation of nasal mucosa cause local hyperplasia of nasal mucosal glands. These hyperplastic glands will cause bulging of nasal mucosa. In addition to glandular hyperplasia changes that occur in the blood vessels will cause oedema in the region of the middle meatus. This in turn increases nasal mucosal oedema. Studies have shown that the number of nasal mucosal glands are the same in polypoidal as in the normal tissue.

Epithelial rupture theory:

This is the currently proposed theory. In this theory the initial stage of nasal polyp formation starts of as epithelial rupture possibly due to inflammation and tissue oedema. This is followed by prolapse of lamina propria through the defect. The adjacent epithelium attempts to cover up the defect there by forming a lining for the polypoidal tissue. If the defect in the epithelium is not covered up real fast the prolapsed lamina propria continues to grow and the polyp complete with its stalk develops. After epithelization of the polyp the characteristic new long tubular glands are formed.



















Figure showing Exudate forming under the nasal mucosa (Exudative theory)


















Figure showing nasal polyp forming after accumulation of exudate


















Figure showing rupture of epithelium














Figure showing development of nasal polyp following epithelial rupture


Role played by mucous glands:

The glandular elements seen in the nasal polypoidal tissue are nasal glands. Commonly seen glands are degenerated long glands. The entire long duct along with their lateral branches are distended due to filled up secretions. Due to the pent up secretion and distention the secretory epithelium of the nasal gland become cuboidal and flat losing their secretory ability. This is followed by degeneration of the gland.

Role played by cellular infilatrates:

Eosinophilic infiltration is an important feature in the pathogenesis of chronic rhinosinusitis and nasal polypi. Accumulation of eosinophils in the polyp stroma is basically caused by increased transendothelial migration, increased survival, and increased concentration of interleukin 5.

Wednesday, February 23, 2011

Role of imaging in nasal polyposis


Introduction:
Imaging plays a crucial role in the diagnosis and management of nasal polypi. The following are some of the important contributions imaging is supposed to make:

  1. It clinches the diagnosis
  2. It helps in evaluation of progression of disease
  3. Helps in surgical planning
  4. Helps in monitoring for recurrence

CT scan is the primary imaging modality used to evaluate patients with chronic sinusitis with nasal polyposis. MRI has only a limited role to play and is used only sparingly. Imaging may be really vital and could even replace diagnostic nasal endoscopy in patients whose nasal cavities are completely filled with polypi and is virtually impossible to perform diagnostic evaluation using a nasal endoscope. This scenario is tailor made for imaging.




CT appearance of nasal polypi:
They appear as rounded bodies of soft tissue arising from the mucosal surfaces of nose and paranasal sinuses. They can be clearly differentiated from the surrounding inflammed mucosal lining and nasal secretion as they are more radio dense and hence appear brighter. Rarely a pedicle attaching the polypoidal mass to the nasal mucosal lining can be seen clearly in the CT scan (pedicle sign). If present it is virtually diagnostic of nasal polypi.
One important point that should be borne in mind while evaluating CT images from a patient with nasal polypi is that they never cause bone erosion. If soft tissue mass arising from the nasal mucosa is associated with bone erosion then it is a definite pointer towards the diagnosis of malignancy. Pressure effects of nasal polyp can be evidently seen in imaging. These effects include local bone remodelling causing a scalloping effect. This scalloping effect should not be confused with that of the scalloping of margins produced by the mucocele since it is always associated with enlargement of the sinus cavity. Rarely this bone remodelling may occasionally cause thinning of the bony septa of the ethmoidal sinus. This thinning could be so extreme that it could go even below that of the resolution of the CT scan. This creates a picture of bone erosion which is not a true one.
Appearance of nasal polyp when contrast CT is taken:
Nasal polypi do not show enhancement on injection of contrast media. The mucosa surrounding the nasal polyi may show enhancement causing an impression of rim enhancement around the nasal polypi.
Types of nasal polyp:
Ethmoidal polypi – arising from ethmoidal sinus and are multiple. They can be visualised in the CT scan of paranasal sinuses as multiple polypoid lesions. Polypi arising close to the cribriform plate area can cause olfactory disturbances.
Polyp arising from the maxillary sinus – is usually solitary. It exits the antrum via the natural / accessory ostium. This causes an enlargement of ostia. Radiologically it appears like a dumbbell because of the constriction present in the midline (ostial exit point). In these patients the medial wall of the maxillary sinus bows into the nasal cavity. This can be clearly visualised in the CT scan images. Obstruction caused by this polyp to the drainage channels of ethmoidal and frontal sinuses (middle meatus) can cause opacification of those sinuses also there by making it difficult to identify the exact origin of the nasal polyp. In this scenario the bone remodelling that takes place in the medial wall of maxillary sinus could be the clincher. If these polyp passes posteriorly to exit via the choana it could be clearly visualized in the axial cuts taken at the choanal level.
Fungal disease may coexist with nasal polypi. If present they could be visualized as hyperdense areas between the nasal polypi shadows.
CT differences between acute sinusitis & nasal polypi:
Acute sinusitis causes a near uniform opacification of the paranasal sinuses whereas nasal polypi inaddition to the opacification show multiple convexities.
Mucous retention cyst can be safely eliminated if the polypo shows a pedicle radiologically. If there is associated bone remodelling then in all probability it could be nasal polyp rather than mucous retention cyst. In case of diagnostic dilemma MRI will clinch the diagnosis.
In cystic fibrosis in addition to the radio densities seen in the CT scan images there is also associated thickening of the maxillary sinus walls due to osteoneogenesis.





















Coronal CT nose and paranasal sinuses showing nasal polyposis with associated bone remodelling



















Axial CT paranasal sinuses showing mucous retention cyst of maxillary sinus


















Coronal CT nose and PNS showing fungal sinusitis involving the maxillary sinus.  Note hyperdense specs could be seen inside the cavity of the sinus in addition to soft tissue opacity

Sunday, February 20, 2011

Squamous cell carcinoma of thyroid diagnostic & management dilemma



Introduction:

Squamous cell carcinoma involving thyroid gland is an extremely rare condition. To label a thyroid tumor as squamous cellcarcinoma the tumor should be entirely composed of tumor cells with squamous differentiation. This condition should be differentiated from:

  1. Papillary carcinoma thyroid containing patches of sqamous epithelium
  2. Anaplastic carcinoma of thyroid containing patches of squamous elements
  3. Adenosquamous carcinoma thryoid which may contain both adeno and squamous elements.


Causes of squamous cell carcinoma thyroid:

  1. Primary squamous cell carcinoma thyroid
  2. Secondary involvment of thyroid gland by tumor extention from adjacent structures
  3. Metastatic involvmement of thyroid gland from adjenct sites like lungs, head and neck, GI tract


Primary squamous cell carcinoma involving thyroid gland is an extremely rare condition affecting about 1% of all the primary thryoid malignancies. Histologically the thyroid gland does not normally contain squamous epithelium that is the reason why this condition is pretty rare. Several hypothesis have been proposed to explain the genesis of squamous cell carcinoma in the thyroid gland.

Goldberg & Harvey theory:
This is one of the earliest theories proposed to account for the development of squmaous cell carcinoma in the thyroid gland. This theory is based on the concept that embryonic remnant of thyroglossal cyst contained squamous elements. Under normal circumstances thyroglossal duct involutes. Persistence of this duct and the related squamous elements happens to be the crux of this theory. Anatomically the lower portion of thyroglossal duct happens to be the pyramidal lobe of thyroid gland. If this theory is true then squamous cell carcinoma of thyroid gland should commonly involve the pyramidal lobe. In reality this tumor is commonly seen in the lateral lobes of thyroid thus puts a question mark on the validity of this theory.


Branchial arch theory:

Branchial arch elements which include ultimobranchial body and thymic epithelium could probably be the source for squamous elements in the thyroid gland.

Metaplastic theory:

This happens to be the more recent one. It says that squamous elements seen in the thyroid gland could have arisen due to metaplasia of normal thyroid cells. Even this theory has its own achilles tendon. The commonest cause for squamous metaplasia in thyroid gland happens to be Hashimoto's thyroiditis. Studies have shown that it is rare for these patients to develop squamous cell carcinoma of thyroid gland.

Gulisano theory:

Gulisano suggested that squamous elements could reach the thyroid gland as direct invasion from adjacent areas like larynx, pharynx and oesophagus. He demonstrated this theory by injecting methylene blue dye in the pyriform fossa before performing thyroidectomy. Superior portion of the thyroid gland was found stained by the dye. This demonstrates that there is a communication between these areas for potential tumor spread.

Clinical features:

Clinically these tumors are very aggressive, infact as aggressive as anaplastic carcinoma. These patients usually present with rapidly increasing neck mass with evidence of involvment of strap muscles, tracheal compression and oesophageal compression.

Role of Imaging:

  1. Allows differentiation of thyroid mass from other neck lumps
  2. Helps in assessing adjacent organs like larynx and oropharynx
  3. Assess oesophageal and tracheal involvement

Prognosis:

Is very poor because of its radioresistance.

Management:

Total thyroidectomy followed by irradiation is the accepted modality. Patients with secondary deposits in the cervical nodes should undergo neck dissection procedures.

Saturday, February 19, 2011

Role of inflammation in nasal polyposis

Introduction:


Nasal polyp is not simple oedema of the mucous membrane of the lateral nasal wall, instead it is a denovo inflammatory growth of the mucosa of the lateral nasal wall in the area of uncinate process and bulla mucosa.
Characteristic features of nasal polyp include:


1. Basal cell hyperplasia
2. Goblet cell hyperplasia
3. Squamous metaplasia (rare)


Features seen in lamina propria:


1. Oedema
2. Lymphocytosis
3. Eosinophils
4. Degenerated cystic glands filled with mucin


Among the above mentioned factors eosinophils, lymphocytes, and oedema of lamina propria play important roles in the genesis of nasal polyp. Studies have demonstrated that risk of developing nasal polyp may be linked to the small arm of chromosome 6. This area of chromosome 6 contains


1. HLA antigens
2. Complement
3. Heat shock protein
4. Proinflammatory gene – TNF α


The HLA genes and the proinflammatory genes are transmitted together from parent to offspring.




Role played by Staph aureus exotoxins in the genesis of nasal polyp:


Exotoxins produced by Staph aureus act as super antigens. They stimulate IgE response against them. The presence of Staph aureus exotoxins and IgE response to them are two potent mediators that could trigger the mucosal lining of lateral nasal wall into developing nasal polyp. Studies have also demonstrated that TNF α levels in patients with nasal polyp was four times more than that present in normal controls. TNF α is a potent immunomediator and proinflammatory cytokine that has been implicated in a large number of human diseases that include nasal polypi, periodontal diseases, irritable bowel syndrome etc.


Cytokines in nasal polypoid mucosa:


The following cytokines have been demonstrated in large quantities in nasal polyp tissue:


1. TNF α
2. IL1-β
3. VCAM – 1
4. RANTES
5. Cotaxin




TNF α and VCAM -1:


TNF α is produced primarily by macrophages and T cells. It was initially known for its antitumor and cytotoxic activity. Studies have now revealed that they play a vital role in evoking inflammatory process. TNF α is known to upregulate VCAM – 1 in fibroblasts present in the nasal mucosa. This upregulation takes place via NF-kβ pathway in the nasal fibroblast. This upregulation of VCAM -1 in the nasal fibroblasts play a vital role in the pathogenesis of nasal polypi. Hence there is a strong rationale in the use of anti NF-kβ drugs in the management of inflammatory nasal polypi. The eosinophils that accumulate in the polypoidal tissue can also synthesize TNF – α causing the vicious cycle to continue. The presence of TNF-α can increase the secretion of chemokines which attracts eosionphils into the polypoidal tissue.
TNF-α increases the secretion of cotaxin and also expression of RANTES from the fibroblasts present in the nasal polypi.


Role of eosinophil changes in alterations of electrophysiology of nasal mucosa:


The substances produced by eosinophils i.e. Eosinophilic mediator and Major Basic Protein increases the permeability of nasal mucous membrane to water. This is caused due to changes that take place in the sodium gate mechanism present in the mucosal cell wall. This excess permeation of water into the nasal mucosa is the cause for mucosal oedema (the most prominent histopathological findings seen in nasal polypi). Polyp epithelia show increased sodium absorption which in turn is followed by water.