Paranasal Sinus Tumors

## **Chapter 5**

## Extensive Tumors of the Frontoethmoidal Region

*Dragan Krasic, Stasa Krasic, Milos Trajkovic and Nebojsa Stojanovic*

## **Abstract**

The frontoethmoidal region is an anatomical complex of the middle and upper mass of the face, placed at the mouth of numerous regions, such as the upper jaw, cranium, orbital and nasal region. The multitude of anatomical elements in a small space with a specific function makes this region very demanding for the diagnosis and treatment of pathological entities. Extensive tumors of this region are a special diagnostic and therapeutic problem. Surgical treatment includes rhinotomy, sinusotomy, orbitotomy, frontectomy, and other types of operations. In the case of skull base extension, the situation becomes more complicated, which leads to the need for the cooperation of several specialists and modification of the surgical technique. A special problem in this region is adequate reconstruction. More specialists perform surgical procedures in these regions. These include maxillofacial surgeons, ENT (ear, nose, and throat) specialists, neurosurgeons, oncological surgeons, and ophthalmologists.

**Keywords:** frontoethmoidal tumors, diagnostic, frontoethmoidectomy, craniotomy, reconstruction, 3D printing, complication

## **1. Introduction**

The nasal cavities are divided in the midline by the nasal septum. Each cavity is wider caudally and narrow cranially. The top of the nasal cavity is made with a thin (0.5-mm) cribriform plate. The floor is the hard palate, formed by palatal extensions of the maxilla and horizontal parts of the palatal bone. The lateral nasal wall includes the maxillary and ethmoid ostia plus three or four turbinates. They are covered with a more voluminous mucous membrane and contain a dense, thick-walled venous plexus. The nasal cavity's upper wall, or roof, consists of olfactory depressions, which are covered with yellowish epithelium, the so-called olfactory mucosa. This mucosa contains bipolar olfactory nerve fibers, which go over the cribriform plate. The connecting axons of the olfactory nerve end freely on the surface of the epithelium, where they spread out like spherical teeth with cilia. Bowman's glands, or olfactory glands, are located in the submucosal layer. Nasal cavities and paranasal sinuses are covered with the Schneiderian mucosa, whereas pseudostratified ciliated epithelium is covered with present goblet cells. Lamina propria, inside the paranasal sinuses,

especially the maxillary, is rich in seromucous glands and can quickly become polypoid due to edema. The goblet component of the cells of the superficial mucosa and seromucous glands is variable. In chronic sinusitis, goblet cells undergo hyperplasia, leading to papillary mucosal lesions [1, 2].

The most significant part of the nasal septum is formed in the form of a rigid plate—the ethmoid bone posteriorly and the septal cartilage anteriorly. The vomer completes the posteroinferior part of the septum. The septum is lined with relatively thin, ciliated respiratory mucosa, which is subject to squamous metaplasia under the influence of irritations. Although the underlying thin lamina propria contains seromucous glands, it is closely attached to the perichondrium and periosteum of the septum [1, 2].

## **1.1 Frontal sinus**

This paired sinus represents a barrier between the frontal cranial fossa and the external environment. The frontal sinus has an anterior, inferior, and posterior wall. The degree of pneumatization varies significantly: from one cell to maximum involvement of the frontal bone. Aplasia is also possible. It is divided by a bone partition into two parts (left and right), and each side is connected to the nose via the nasofrontal duct. The posterior wall is the anterior wall of the anterior cranial fossa, and the lower wall forms part of the upper wall of the orbit. The front wall is the frontal bone (**Figures 1** and **2**) [1].

**Figure 2.** *Ethmoidal sinus.*

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

#### **1.2 Ethmoid complex**

According to the location of their ostium, the ethomoidal paired sinus complex contains 3–18 cells grouped as anterior, middle, and posterior. There is an inverse relationship between the number and size of cells. Generally, posteriorly sided cells are more numerous and petite than anterior cells. Each ethmoidal labyrinth is located between the orbit and the superior nasal fossa. The left and right groups of ethmoidal cells are connected in the midline by the ethmoid bone's cribriform plate (nasal roof). In evaluating sinus-nasal tumors, the cribriform plate is a crucial feature. The cribriform plate involvement implies direct tumor extension into the anterior cranial fossa. The crista galli is a characteristic bony feature that extends from the midline on the cribriform plate up into the floor of the anterior cranial fossa. The medial wall of each ethmoidal labyrinth is formed by a thin bone lamella from its origin in the middle, just above the nasal concha. The lateral ethmoid wall contains a thin lamina papyracea that divides the ethmoidal cells from the orbit. That is another important landmark for tumor expansion. The roof of the ethmoid complex builds the fovea ethmoidalis [1, 2].

For a better understanding of the clinical presentation and modalities of treatment of extensive lesions of this region, it is essential to have a good knowledge of the anatomy of the anterior cranial fossa [3].

#### **1.3 Anterior cranial fossa (fossa cranii anterior)**

The frontal, ethmoid, and pterygoid bones take part in the formation. The front wall forms the back wall of the frontal sinus, the back wall forms the anterior sphenoid process, and the frontal bone externally limits it. The frontal bone forms the largest part of the anterior cranial fossa. In its middle line, there is the frontal ridge (crista frontalis) for the attachment of the cerebral falx (falx cerebri), and below the ridge, there is a blind opening (foramen cecum) where part of the dura mater is drawn in, and which represents a place of communication of the draining veins of the nasal cavity and the sagittal sinus. To the left and right of the midline, there are finger-shaped depressions caused by the convolutions of the cerebrum. The highest point is the rooster's crest (crista galli) of the ethmoid bone, which is the attachment of the cerebral falx. The crista galli is surrounded by the cribriform plate (lamina cribrosa), which serves for the passage of fibers of the olfactory nerve (filia olfactoria). The olfactory bulb (bulbus olfactorius) lies both on its left and right sides (**Figures 3** and **4**) [2, 3].

Left and right of the front part of the cribriform plate, there are two openings each for the passage of anterior ethmoidal blood and nerve vessels. Under the cribriform plate, there are, on both sides, the left and the right labyrinth filled with ethmoidal cells, which together form the ethmoid sinus. Pathological entities of the ethmoid sinus easily penetrate the skull through the cribriform plate, which is very thin and porous.

As for the extracranial part, the most important anatomical structures below the anterior cranial fossa are the frontal and ethmoid sinuses, which were described earlier, as well as the orbit.

The bony orbit is often a route for the intracranial or extracranial spread of tumors or infections due to its proximity to the skull base. The bones that form the base of the skull also participate in the formation of the orbit. Thus, the orbital plate of the labyrinth of the ethmoid bone and the body of the pterygoid bone participate in the

construction of the inner wall, whereas the outer wall is built by the orbital surface of the great wing. The eye cavity communicates with the intracranial fossa via the optic canal and the upper orbital fissure and the lower orbital fissure with the pterygopalatine and infratemporal fossa. These openings represent important surgical markers when resecting tumors of the anterior cranial fossa. On the medial wall of the eye cavity, there are openings for the anterior and posterior ethmoidal arteries, and these are important surgical markers for the localization of the optic canal (located 0.5 cm behind the opening of the posterior ethmoidal artery) (**Figure 5**) [3].

## *1.3.1 The anterior cranial fossa consists of*

1.Meninges – The relationship between the skull bones and the dura mater is particularly important. It attaches to the frontal ridge and the crista galli, forming a duplicate in which superior and inferior sagittal sinuses are located and to which special attention should be paid when resecting tumors of this area. These sinuses *Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

communicate with the veins of the nasal cavity via the foramen cecum. The presence of such a channel between two cavities can lead to developmental anomalies: nasal dermoid cysts, nasal gliomas, encephaloceles, and meningoencephaloceles [3].


#### **1.4 Vascularization**

Vascularization of the nose and paranasal cavities originates from internal carotid artery (a. carotis interna) (ethmoidal anterior and posterior arteries from ophthalmic artery (aa. ethmoidales anteriores et posteriores from a. ophthalmica)) and external carotid artery (a. carotis externa): sphingopalatine artery (a. sphenopalatina), infraorbital artery (aa. infraorbitales), and aa. alveolar artery (alveolares) (branches of maxillary artery (a. maxillaris)), superior labial artery (a. labialis superior) (from facial artery (a. facialis)), and aa. pharyngicae. Venous blood drains through the anterior, upper, and posterior groups of veins (facial vein (v. facialis), superior ophthalmic vein (v. ophthalmica sup.), and pterygoid plexus (plexus pterygoideus)). Due to the anatomical connections of the veins of this area (directly via the ophthalmic vein and indirectly via the pterygoid plexus and rete foraminis) with the cavernous sinus, their clinical significance is great. The mucous membrane of this region is innervated by the sensitive nerves of the I and II branches of the trigeminus. Lymph drains into the submandibular and deep lymph nodes of the neck [1–3].

## **2. Physiology**

In physiological conditions, there is a need for a permanent and specific relationship between upper and lower airways, both anatomically and functionally. Everything is subordinated to the fact that the air reaches lung alveoli smoothly for a successful exchange of gases of necessary qualities (appropriate temperature, humidity, purity, etc.). Both from the anatomical and functional points of view, there is a unity between the two stages of the airway. The violation of the unity of function leads to various pathological conditions. Clinically, there are known diseases that might develop, especially due to chronic nasal obstruction. These are recurring inflammatory processes that occur in the mucous membrane of the pharynx, throat, trachea, and bronchi. These recurring inflammatory processes lead to chronic inflammatory processes in the lower respiratory tract with all the consequences. Hence, the great importance of normal nasal function for the condition of the lower respiratory tract. It is not uncommon for chronic nasal obstructions (distorted nasal septum, nasal polyposis, etc.) to be present in some individuals with asthmatic bronchitis or bronchial asthma. The nose has numerous essential functions on which the functions of many other organs directly and indirectly depend. The following are responsible for the normal performance of these functions: normal anatomical relations of the front and back nostrils and nasal cavities, the condition of the nasal mucosa with all its elements, both respiratory and olfactory, the autonomic nervous system, as well as a series of reflexes [2, 3].

## **3. Embryology**

The embryonal development begins prenatally, continues throughout childhood, and is completed only around the age of 20. The paranasal sinuses communicate with the respiratory region of the nasal cavity via narrow openings. They have the same histological structure as the nose's respiratory region; only the lamina propria is somewhat thinner. The mucus created in this region is drained into the nasal cavity by coordinated movements of the kinocilium [2].

## **4. Epidemiology**

Tumors of this region designate a rare group of tumors that tend to grow along eclectic regions of the cranial base. Although rare, these tumors are potentially life-threatening and have long been assumed inoperable due to their sensitive place and possible brain and sensory injury (mainly sight, smell, hearing, and balance). Nowadays, these lesions are operable, and with modern imaging techniques, a multidisciplinary approach, and increasingly successful techniques, impossible has become a "relative" term.

Sixty percent of sinus-nasal tumors originate from the maxillary sinus, 20–30% from the nasal cavity, 10–15% from the ethmoidal sinus, and 1% from the sphenoid and frontal sinuses each. They are more frequent in men, with a maleto-female ratio of 5:1 and show the highest incidence in the 5th and 6th decades of life [4–6].

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

## **5. Etiology**

Some etiological factors, such as tobacco smoke and specific occupational exposures, increase the risk of sinonasal tract malignancy development. It is presumably correspondingly valid for the frontal sinus: workers in the nickel industry had 28 times higher incidence of squamous cell carcinoma in comparison to the general population; tanners, who are in contact with tannins and chromate; carpenters, who are exposed to formaldehyde-based adhesives, wood dust, and preservatives such as creosote, have a 500-fold increased risk of adenocarcinoma development [5–7]. People in the textile industry, oil refinery workers, welders, blast furnace workers, and people exposed to ionizing radiation had a growing frequency of malignant diseases of paranasal sinuses [8]. Thorotrast (thorium dioxide) exposure, a radioactive contrast agent typically infused into maxillary sinuses until the 1950s, was related to the development of maxillary and frontal sinus carcinomas after a median latent period of roughly 15 years [6].

## **6. Clinical symptoms**

The medical history requires data on the onset, duration, course of the disease, subjective complaints, and previous treatment. The patient will likely exhibit frontal headache, visual disturbances such as loss of vision in one eye, nasal obstruction, hyposmia, or anosmia. If tumors are larger, ptosis, paralysis, amyloidosis, unilateral blindness, or even exophthalmos can be observed. Clinical examination should include nose and nasopharynx inspection. If there are ophthalmological disorders, the patient should be referred to an ophthalmologist to assess the clinical picture and determine the vision state [6, 7, 9].

## **7. Diagnostics**

Tumor diagnosis requires a carefully taken medical history and a detailed clinical examination using auxiliary procedures (X-ray techniques, laboratory examinations, and biopsy). Computed tomography (CT), nuclear magnetic resonance (NMR), angiography, three-dimensional (3D) stereolithography (SLA), and 3D printing are used to show the tumor, its size, and its relationship with surrounding structures [10].


waves, which are absorbed by detectors and converted into an image by the computer. NMR is superior to CT in soft tissue tumors and when it is necessary to delineate various soft tissue structures, which is particularly important in the frontoethmoidal region. Intravenous administration of a contrast medium improves the visibility of soft tumors. It is considered harmless, unlike CT [10].

• Angiography is an X-ray method that helps visualize blood vessels. In surgery, it is used to diagnose malformations and tumors of blood vessels and to assess the relationship with large blood vessels. Interventional angiography is performed using the endovascular approach for preoperative embolization of vascular tumors (juvenile angiofibroma, hemangioma, and meningioma) [10, 11].

Nowadays, the surgical team is becoming more reliable due to the possibility of visualization using a 3D radiology CT scanner and software that allows the surgeon to simulate the planned operation only with 3D movements of bony elements. Although the next generation of surgeons will undoubtedly master the 3D virtual surgical simulation, composite digital 3D treatment of the face, i.e., of the skeletal model, is needed for precise virtual surgical planning. This requires constructing a composite model based on data from 3D sets: cone-beam computed tomography (CBCT), and 3D photography, representing 3D stereolithography [12–15].

First, the data from the CBCT scanner are entered into the software for virtual surgical planning. Then the anatomical structures are segmented. This includes emphasizing the shape of the structures visible on cross-sections of the already obtained data. Hard and soft tissues are separated. Anatomical components, such as the skull, soft tissue, nerve canals, and airways, are structurally defined as independent elements. To provide a more realistic appearance of the face with color and texture, CBCT scanning is added along with 3D images. This completes the creation of the patient-specific composite model. An osteotomy is simulated by splitting the bone using a cutting tool. After the virtual sectioning of the patient's skeleton, different parts of the bone can be repositioned in the appropriate desired position, with osteosynthetic material modeling, which later shortens the surgical intervention (**Figure 6**) [12, 16–22].

**Figure 6.** *The use of software for surgical planning.*

## **8. Differential diagnosis**

First, the differential diagnosis must exclude infectious, traumatic, congenital, and vascular lesions, as well as tumors. Due to the proximity of paranasal sinuses to the intracranial content, infections are a frequent cause of changes in the base of the skull. Infections can be acute, such as acute bacterial sinusitis, or they can have a milder chronic course: petrositis or chronic sinusitis. Aggressive forms of infection are seen in people with a weakened immune system, diabetics, cachexic individuals, and individuals on immunosuppressive therapy. Infections can lead to intracranial complications: meningitis, brain abscess, and venous sinus thrombosis.

Cranial trauma should be considered separately. After cranial trauma, often after healing, there can be leakage of the cerebrospinal fluid and dysfunction of cranial nerves or the formation of epidural and subdural hematomas that compress the brain.

Congenital lesions often have to be surgically resected employing methods used to approach skull base tumors. Congenital encephaloceles and meningoencephaloceles are usually present in the nose, whereas primary congenital cholesteatoma (PCC) is present in the petrous bone, PCC, or anterior cranial fossa. Vascular malformations can also involve the base of the skull [6, 7, 22].

## **9. Biopsy**

Biopsy of tumors of the frontoethmoidal region usually requires trepanation of the floor of the frontal sinus when the disease does not involve the nasal cavity or ethmoid sinuses. This can be attempted endoscopically but may require an external approach. It is rather challenging, considering many vital anatomical elements in a small space [7, 22].

## **10. Classification of tumors of the frontoethmoidal region**

See **Table 1**.

## **10.1 University of Florida clinical stages**

Stage I: tumors limited to the site of origin;

Stage II: spread to adjacent sites (orbit, paranasal sinuses, skin, nasopharynx, pterygomaxillary fossa);

Stage III: destruction of the skull base or pterygoid process and/or intracranial propagation.

At the time of diagnosis, most malignant tumors of the frontoethmoidal region are stage II or III. Regional and distant metastases occur in patients with malignant tumors in this region in 10–15 and 10%, respectively [23]. Despite advances in craniofacial surgery and multimodal therapy, local recidivism represents the most meaningful cause of treatment failure and death. It seems that the histological stage and the spread of the disease are directly related to the prognosis of tumors in this region [23, 24].


#### **Table 1.**

*2022 5th edition of the World Health Organization (WHO) classification of Tumors of the nasal cavity, paranasal sinuses, and skull base [23].*

## **11. Benign tumors**

In addition to the above-mentioned tumors, numerous benign changes may also occur in this region, which, due to the multitude of anatomical details and a large specific region, may represent a great surgical problem. These include:

#### **11.1 Osteoma**

These are benign, slow-growing tumors made of compact bone. The predilection place for their formation is the paranasal sinuses, primarily the frontal. They are most common in the fifth and sixth decade of life, predominantly in men. They present symptoms late and are usually diagnosed as incidental findings. X-rays present them as intense, oval shadows. They may occur in Gardner's syndrome (multiple osteomas, skin fibromas, and colonic polyposis). Given the benign nature and absence of recurrence, the therapy is peripheral osteotomy (**Figure 7**) [21, 22, 25].

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

#### **11.2 Chondroma**

Chondroma is a benign tumor originating from hyaline cartilage. It may develop centrally or peripherally in the bone. They are rarely found at the base of the skull. They are slow-growing, encapsulated, oval tumors of hard elastic consistency. They can grow into the surrounding tissue, which explains the tendency toward relapses. There is a risk of malignant alteration. Radiologically, they are presented in the form of an oval light in the bone. The therapy is surgical. In larger tumors, bone resection is indicated due to the risk of recurrence and malignant alteration [24, 26].

#### **11.3 Vascular lesions**

Hemangiomas are the most common vascular tumors. They are benign head and neck tumors in children. They may lead to significant esthetic and functional disturbances. The growth is always infiltrative, but there is no risk of malignant alteration. The tumor is usually present at birth, and after the phase of initial growth, it spontaneously involutes in over 90% of cases. Histologically, capillary and cavernous hemangiomas are distinguished.

Vascular malformations, structural abnormalities of blood vessels, exist mainly at birth, grow together with the patient, and do not show a tendency toward involution, often affecting the bone as well. Sturge-Weber syndrome (SWS), i.e., encephalotrigeminal angiomatosis of the facial skin and leptomeninges. With the help of echography, CT, and angiography, it is possible to determine the presence and extent of the lesion, which has prognostic significance. Therapy is difficult and often unsuccessful [24, 26].

## **11.4 Dermoid and epidermoid tumors and cysts**

They occur more often in children. The growth of cysts leads to bone thinning and compression of brain tissue. These formations have a thin capsule; therefore, recurrence is quite common. The wall of epidermoid cysts consists of the outer parts of the skin, whereas the wall of dermoid cysts consists of deeper layers of the skin, and skin adnexa can be found in their lumen. The therapy is surgical (**Figures 8** and **9**) [24, 27, 28].

## **11.5 Meningioma**

Meningiomas originate from meningothelial cells and make up about 20% of all primary intracranial tumors. They are mostly benign lesions, however, there is a possibility of malignant alteration. They occur more often in the elderly and are extremely rare in children. The lesions are thought to be genetically determined. The only known nongenetic factor is radiation exposure. Symptoms depend on the size of the lesion and usually develop in accordance with the degree of compression of brain structures. They are usually classified according to localization:


**Figure 8.** *Cystis epidermalis.*

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

**Figure 9.** *Pyocela reg. Frontoethmoidalis.*

sphenoid or cavernous sinus. A special type of meningioma may appear in this place in the form of plaque (en plaque);


Most meningiomas are nodular and compress adjacent structures. They are all encapsulated and attached to the dura, from which they receive vascularization. Hyperostosis of the bone is present beneath the meningioma. Based on cellularity, cytological atypia, mitosis, and necrosis in the tumor are divided into typical, atypical, and malignant.

Less common histological subtypes are syncytial, fibromatous, transitional, and psammomatous meningiomas. Secretory meningiomas secrete vascular endothelial growth factor (VEGF), so they are associated with extensive brain edema (**Figures 10** and **11**) [24, 28].

**Figure 10.** *Meningeoma frontoetmoidoorbitalis recidivans. Reconstructio def. Cum Peeck opima impl.*

## **11.6 Fibrous dysplasia**

Fibrous dysplasia is a rare bone disease characterized by the replacement of bone with benign fibrous tissue. It may affect a single bone (monostotic fibrous dysplasia) or multiple bones (polyostotic fibrous dysplasia) in the human skeleton. Monostotic fibrous dysplasia is much more common than the polyostotic variant. Fibrous dysplasia that affects several adjacent bones of the face and head is considered monostotic and is then called craniofacial fibrous dysplasia. Fibrous dysplasia occurs as part of

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

**Figure 11.** *Exreacranial meningioma in synus ethmoidalis et cavi nassi recidivans.*

McCune-Albright syndrome, characterized by multiple white coffee-colored (fr. caféau-lait) melanin pigmentation of the skin or mucous membrane and hyperfunction of one or more endocrine glands.

Clinical picture – Patients with craniofacial fibrous dysplasia complain of painless swelling and facial asymmetry. In children with café-au-lait freckles, the abovementioned syndrome should be ruled out.

X-ray findings – Radiographic findings of fibrous dysplasia show vaguely circumscribed bone changes with a characteristic "milk glass" appearance. Lesions gradually move into the adjacent normal bone; therefore, it is difficult to determine their border. Computed tomography (CT) is the method of choice for diagnosing this disease, which provides accurate insight into the affected areas and enables the planning of surgical procedures through three-dimensional reconstruction.

Histological finding – Microscopically, fibrous dysplasia shows the replacement of normal bone by cellular fibrous tissue.

Therapy – Fibrous dysplasias usually stop growing after skeletal maturation; therefore, it is best to postpone surgical therapy until the skeleton has been completely formed. Surgical correction (without removing the entire change) is performed in cases of permanent, deforming growth or for esthetic and functional reasons. The prognosis is good, they rarely exhibit malignant alterations and when they do, they usually develop osteosarcoma (**Figure 12**, [24, 28]).

**Figure 12.** *Dysplasio fibrosa recidivans.*

## **12. Sinonasal papillomas**

## **12.1 Inverted papilloma**

(Schneiderian papilloma, inverted type) can affect the frontal sinus in 11–16% of patients and is associated with malignant transformation into squamous cell carcinoma in 5–15% of cases [29]. Rarely, an inverted papilloma may arise from the frontal sinus [28].

Etiology – Epstein-Barr virus and human papillomavirus have been proven to play a significant role in its development. It is more common in men, occurs primarily in patients aged 40–70 years, and is associated with allergies, inflammation, and smoking.

Localization: Inverted papillomas most often appear on the nose lateral wall in the region of the middle nasal concha or ethmoid cavity and often spread into sinuses, especially maxillary and ethmoid, or sphenoid and frontal sinuses, but to a lesser extent. Even though they are described predominantly as unilateral, rare cases of bilateral papillomas have been reported in the literature. As for clinical characteristics, nasal obstruction dominates. Other manifestations include impaired nasal drainage, headaches (especially frontal), epistaxis, anosmia, lacrimation, proptosis, and diplopia. Conversely, pain is felt in approximately 10% of cases. However, when present, a secondary infection or malignant transformation should always be suspected.

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

Clinically, an inverted papilloma presents as a rosy or gray, opaque, soft, polypoid swelling with an uneven surface.

Radiologically, it varies with the degree of the disease. In the early stage, it may only be of soft tissue density within the nasal cavity and/or paranasal sinuses. Later, with the spread of the disease, it is characterized by one-sided shading and thickening of the mucosa of one or more sinuses, as well as by the expansion onto adjacent structures. Erosion and pressure on the bone may be apparent and must be differentiated from destructive invasion associated with malignancy, such as *de novo* carcinoma.

#### **12.2 Differential diagnosis**

Differential diagnosis includes nasal polyp with squamous metaplasia, respiratory epithelial adenomatoid hamartoma (REAH), and invasive carcinoma.

While inverted papilloma of the frontal sinus can be treated endoscopically, the presence of a malignant tumor requires external, *en bloc* resection [11, 20, 30].

#### **12.3 Oncocytic papilloma (Schneiderian papilloma, oncocytic type)**

Oncocytic papilloma emanates from the Schneiderian membrane and is formed of ectopic sheets and endophytic intussusceptions arranged in multiple layers of cells with oncocytic features. Intraepithelial mucin and neutrophil-content microcysts are the main features of this lesion. Oncocytic papilloma is equally distributed between the sexes and occurs in patients older than.

## **13. Unlike inverted papilloma, HPV was not identified in oncocytic papilloma**

The localization of the oncocytic papilloma is almost always unilaterally on the lateral wall or in the sinuses, usually maxillary or ethmoidal. It may remain localized or rarely extend into the adjacent structures, such as the orbit or skull.

The epithelium has a characteristic appearance and contains numerous small cysts overfilled with mucin or neutrophil content (microabscesses). The stroma varies from edematous to fibrous and may comprise a limited number of lymphocytes, plasma cells, neutrophils, and eosinophils. Seromucous glands are insufficient.

Four to 17% of all oncocytic papillomas are harborers of carcinoma. Most of the papillomas are not only squamous but also mucoepidermoid. Small cell carcinoma and sinus-nasal undifferentiated carcinoma are possible.

The prognosis depends on the histological type, invasion degree, and tumor size. In some cases, carcinoma *in situ* is of little consequence to the patient, while others are locally aggressive and can metastasize. Clinical behavior is identical to that of inverted papilloma. If inadequately removed, there is at least 25–35% recurrence, usually within 5 years [11, 31].

## **14. Malignant tumors**

#### **14.1 Squamous cell carcinoma**

*Squamous cell carcinoma* is the most common malignant tumor, accounting for 90% of all the cases in the frontoethmoidal region [6]. Bone erosion with hyperostosis has been described in 48% of cases, and the incidence of bone involvement may be misjudged, given that most of the literature-described cases predate CT scanning [9, 27]. Clinical presentation may mimic mucocele with swelling of the upper eyelid and forehead skin. However, there is usually no evidence of infection, and the degree of bone destruction and hyperostosis has been described as disproportionate to sinus expansion [6, 9, 27].

Carcinomas localized in the ethmoid area rapidly give a clinical picture of endocranial expansion and an ophthalmologically clinical picture. They are reflected in the protrusion of the bulbus, most often downward and laterally, with the displacement of the bipupillary line seen horizontally. Various degrees of eyelid ptosis are present. All this is accompanied by diplopia of varying degrees, pain when moving the bulbus, and headaches.

**Figure 13.** *Ca planocellularae non kerathodes ethmoidalis.*

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

The 5-year survival rate of patients with squamous cell carcinoma of the paranasal cavities is between 25 and 50%. Patients with squamous cell carcinoma of the frontoethmoidal region had poor prognosis, and most patients are in a progressive disease stage **Figure 13** [28, 30].

A combined treatment modality consisting of radical surgery with postoperative radiation is most often applied, and radiation, as monotherapy, is reserved for patients with inoperable disease [28]. Limited data support the use of adjuvant chemotherapy in treating sinus carcinoma. However, due to favorable results observed with adjuvant chemotherapy elsewhere in the head and neck, chemotherapy simultaneously with radiation should be considered [29, 32].

The most common forms of squamous cell carcinoma are the following:

#### **14.2 Nonkeratinizing**

(Cylindrical cell, transitional) carcinoma—this is a particular tumor of the sinus-nasal tract characterized by a plexiform or banded growth pattern. It resembles and is very similar to urinary tract carcinoma. Cytological atypia is present to a significant extent. As its name suggests, this tumor has no keratinization, although a certain degree can be seen. The tumor can be moderately or poorly differentiated, which is difficult to recognize as squamous, and has to be differentiated from olfactory neuroblastoma or neuroendocrine carcinoma **Figures 14** and **15** [33, 34].

**Figure 14.** *Ca planocellularae nonkeratinizing.*

**Figure 15.** *Nonkeratizing cell Ca.*

## **14.3 Basaloid squamous cell carcinoma and verrucous carcinoma**

Originate from the sinonasal tract. Basaloid squamous cell carcinoma is a rare tumor of the paranasal sinuses. It has been only described in sporadic literature cases (only 14 case reports), and none of the patients has basaloid squamous cell carcinoma in the frontal sinus [28]. A histologically separate variant of squamous cell carcinoma, basaloid squamous cell carcinoma is an aggressive, high-grade tumor that is profoundly invasive, multifocal, and frequently metastatic, with a poor prognosis in the advanced stage.

Contrary to the previous ones, *verrucous carcinoma* is a low-grade squamous cell carcinoma type related to a more promising prognosis and outcome when assertive treatment is used.

Verrucous carcinoma rarely affects the frontoethmoidal region, and despite low-grade histology, intracranial extension is the rule that emphasizes the need for aggressive treatment in such cases, despite more favorable histology (**Figure 15**) [28].

### **14.4 Adenocarcinoma**

*Adenocarcinoma* is the second most frequent malignancy of the frontoethmoidal region, accounting for around 10% of patients. Compared to squamous cell carcinoma, it is associated with a better prognosis. The 5-year survival rate for patients with adenocarcinoma of paranasal sinuses ranges from 40 to 60%. Multimodal therapy, including surgery and radiation, is the most commonly prescribed. Adjuvant chemotherapy has a beneficial effect on disease control, with impressive local responses. The prognosis for patients with disease limited to the frontoethmoidal region is unknown due to a scarce number of cases (**Figure 16**), [11, 30, 31].

*Adenoid cystic carcinoma* of frontal sinus origin may concern the frontal sinus due to direct spread from the ethmoid cells. An increased incidence of local recidivism and distant metastases is associated with poor long-term prognosis in patients with adenoid cystic carcinoma of paranasal sinuses. The 5-year survival rate ranges

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

#### **Figure 16.** *Adenoca sinuss etmoidalis ad orbitam penetrans.*

between 17 and 53%, with 50% of local recurrence, 20% of regional recurrence, and 30% of distant metastases [30, 35]. Three different histological variants were described: cribriform, tubular, or solid; local recidivism is pronounced in the solid tumor variant. However, most tumors have a mixture of regional recurrence in 20% and distant metastases in 30% [21, 36, 37].

Aggressive surgical resection combined with postoperative radiation improves local control rates but does not influence the survival rate due to the high frequency of distant metastatic disease [37]. Perineural invasion is a characteristic of this tumor, and it has been described in more than 90% of paranasal sinus lesions. The correlation between perineural invasion and local disease control has not been defined **Figure 17** [36, 37].


Conservative treatment, chemo- and radiotherapy are only prescribed in patients with lymphoma. Unfortunately, sinonasal non-Hodgkin's lymphomas might be less responsive to traditional chemoradiation regimens.

The role of surgery is limited to tumor biopsy and diagnosis-making and can often be achieved endoscopically, although an external approach may be required to obtain suitable tissue (**Figure 19**) [31].

**Figure 17.** *Ca verucosum.*

**Figure 18.** *Fibrosarcoma reg frontalis ad sinuss frontalis penetrans.*

In the frontoethmoidal region, plasmacytomas and metastases of primary tumors from the breast, lungs, and kidneys are observed [8, 38, 39]. Plasmacytoma responds to either surgery or radiation therapy, and disseminated disease is treated with chemotherapy. Solitary metastases are treated surgically. Overall, 10-year survival rate is 50%. Metastases to the frontoethmoidal region from distant organs have a poor prognosis (**Figure 20**).

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

**Figure 19.** *Non-Hodgkin lymphoma B-cell nodal diffusion.*

**Figure 20.** *Hystiocitoma malignum synus ethmoidalis rec.*

## **15. Surgical approach**

## **15.1 Endoscopic approaches**

Endoscopic approaches to the frontoethmoidal region have been frequently and successfully used to treat the benign disease. More data on endoscopic approaches' results in treating malignant diseases in this region need to be collected. Additionally, the endoscopic approach could be performed to biopsy inferiorly or medially based tumors or the nasofrontal canal tumors. However, an open approach is necessary

for surgical extirpation of malignant tumors. The surgical approach depends on the extent of required resection.

Rare cases of early tumors restricted to the frontal sinus with intact bony walls or located in the lowest part of the frontal sinus or nasofrontal recess can be approached through a *limited external incision* [20].

The surgical access is achieved via an incision 2–3 cm above the medial part of the upper eyelid, just below the eyebrow, and medial to the supraorbital nerve in the superomedial part of the orbit to expose the frontal sinus floor. The periosteum is raised, and the bottom of the frontal sinus can be entered with a drill.

1.*Lynch approach and gull wing*. When visualization of the anterior ethmoid or nasofrontal recess is demanded, *Lynch frontoethmoidectomy* could be performed, which extends through the eyebrow medially and inferiorly to the level of the middle canthus and can be extended laterally to the lateral eyebrow side. This approach preserved the integrity of the supraorbital neurovascular bundle in case the anterior wall or the frontal sinus floor is intact. When the tumor involves the intersinus septum and access to the contralateral frontal sinus is required, a *gull-wing incision* can be performed, i.e., a horizontal incision across the root of the nose connecting the incision with the contralateral Lynch incision. These approaches are also used for biopsy, when it is impossible to perform endoscopically (**Figures 21** and **22**) [4, 10, 11, 22].

**Figure 22.** *Gull-wing incision.*

**Figure 21.** *Lynch.*

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*


**Figure 23.** *Lateral rhinotomy.*

**Figure 24.** *Weber-Ferguson.*

**Figure 25.** *Orbit exenteration.*

Bearing that the largest number of tumors is detected in stages II and III, approaches for the front base of the skull are used to radically remove the tumor and perform adequate reconstruction [33, 37]. There are different surgical approaches to the skull base:


Since the days of Galen, the principles of surgical cancer therapy have remained the same. Complete *en bloc* excision of the tumor is essential. The main characteristics of each tumor approach are the following:


## **15.2 Anterior craniofacial resection**

Bicoronal incision, which connects the tips of both auricles, allows access to the frontal cranial fossa and structures in its proximity (ethmoid sinuses, upper nasal septum, roof of the orbit, and frontal sinus). When performing an incision near the auricle, it is necessary to take care of the bifurcation of superficial temporary artery (a. temporalis superficialis). The tissues of the scalp, galea aponeurotica, and cranial periosteum are well vascularized by both temporal and supraorbital blood vessels, so separate flaps of the periosteum or galea can be used, if necessary. The bone above the frontal sinus, the squamous part of the temporal bone, and the parietal bone are diploic and less resistant to infection than the thin membranous bone of the frontal plate of the frontal sinus. The dura is the thinnest over the planum and jugum sphenoidale, it is firmly attached to the frontal bone, especially over the frontal crest and crista galli, so it is most susceptible to injury in those places when lifting from the base of the skull. The upper sagittal sinus is located in the midline on the duplicature of the dura, and olfactory nerves penetrate the dura at the level of the lattice plate. Resection of these nerves almost irreversibly leads to leakage of the cerebrospinal fluid and postoperative rhinorrhea [31]. In the orbit, the anterior and posterior orbital arteries

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

penetrate the base of the skull between the ethmoid and the frontal bone. The optic nerve lies 3–7 mm behind the opening of the posterior ethmoidal arteries. The optic chiasm is the posterior border of resection of the anterior cranial fossa and is located above and medial to the cavernous sinus. During the intervention, the content of the cavernous sinus, as well as ophthalmic artery (a. ophthalmia), is subject to damage, which leads to blindness [33, 37].

## **15.3 Operative technique**


tomy, rhinectomy, or facial skin excision. However, compared to exenteration patients undergoing periosteal resection with eye preservation, eye preservation surgery is not associated with a worse outcome, suggesting that the orbit can be preserved in such cases [9, 31]. Tumors that invade the periorbita have a higher potential for invasion and a worse prognosis. Periorbital involvement is traditionally considered an indication of orbital exenteration. However, several studies have proposed that limited periorbital involvement can be resected while preserving the orbit, with extempore biopsy to achieve negative margins without compromising the outcome [33, 37]. The consequences associated with preserving the orbit may be acceptable to patients considering the esthetic value of the preserved eye, especially when part of the functional vision can be preserved. Many surgeons consider bilateral orbital exenteration a contraindication for surgical resection.

Next, a nasal osteotomy and a contralateral external incision of the ethmoid are performed, and the periorbita is raised along with the coagulation of ethmoidal blood vessels (they mark the ethmoid roof). The bicoronal flap is lowered, and the brain's frontal lobe is retracted. The procedure is performed under the watchful eye, simultaneously through facial and intracranial resection [32, 33].

#### **15.4 Craniofacial resection**

Craniofacial resection continues simultaneously through both incisions. Depending on the extent of the tumor, the removal of the bone of the base of the skull, the ethmoid complex, and the passage back to the sphenoid sinus, which is approached transcranially between the optic nerves, is performed [32, 33].

## **16. Intraoperative reconstruction**

The reparation of the dura is usually performed by using sutures or plastic flaps. The orbital wall reconstruction is recommended for subtotal or total floor defects, defined as greater than 80% of the surface or multisegmental defects. The function of the preserved eye is significantly worsened due to postoperative radiation. In one extensive group of patients undergoing orbital preservation surgery, radiation-induced blindness occurred in the ipsilateral eye in 35% and the contralateral eye in 8% [33].

The galeal-pericranial flap can cover defects of the anterior cranial fossa. Stabilization of craniotomy and orbital bone grafts is achieved with titanium plates or meshes. Larger dural defects heal with free microvascular flaps.

## **17. Closing the wound**

The basal subfrontal and subtemporal infratemporal approaches are used for lesions with a greater spread in the sphenoid, ethmoid, and medial parts of the cavernous sinus. The advantage of this approach is the possibility of using the galeal frontalis flap in addition to the temporal muscle flap. Disadvantages include prolonged operation time and loss of smell (**Figures 26** and **27**) [32].

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

**Figure 26.** *Bicoronal approach with an intracranial view.*

## **18. Reconstruction of skull base defects**

The reconstruction of skull base defects after the removal of the tumor is an extremely important factor because the base of the skull is an important barrier and protection of the intracranial content. The primary goal of the reconstructive phase is to reestablish the anatomical impermeable membrane between the splenium and the neurocranium. This implies the reconstruction of the dura and the continuity of the cranial base. Simultaneously, the protection of the exposed internal carotid and closure of the pharynx and paranasal sinuses are achieved. Once this is established, attention is paid to setting up the contour of the craniofacial skeleton with great emphasis on facial function and esthetics. External soft tissue coverage completes the reconstructive phase.

During osteotomy, the craniofacial bone is removed to allow access to the tumor with minimal brain retraction. Osteotomies are performed during the surgical approach in tumor-free zones. After osteotomy, bone fragments are joined and fixed with mini plates. Another type of defect is caused by the removal of the tumor from the base of the skull and the corresponding craniofacial skeleton. Generally, these defects are reconstructed using a bone graft but are filled with soft tissue flaps (pericranial flap, temporal muscle, and microvascular flap). In case of large defects at the front base of the skull, bone reconstruction can be done. Cranial bone grafts

have proven to be excellent sources of bone material and exhibit the lowest percentage of bone resorption. Bone defects after tumor removal can be filled with a soft tissue flap (pericranial, temporal, pectoral, latissimus dorsi flap, pectoral flap, etc.). Dural defects are closed with sutures, fascia (usually fascia lata), and larger defects with myocutaneous flaps. Drain placement is an essential part of postoperative management. Proper placement of drains allows drainage of possible hematomas or seromas and prevents the formation of a cerebrospinal fistula. Drains are placed so that the drainage is guided by gravity.

The development of science has led to the fact that we can now make an individual model of the skull based on 3D stereolithography, perform an operation on the model, and based on the resulting defect, which is scanned, print an individually created material for the reconstruction of this area using a 3D printer. Applications vary from anatomical models (mainly for surgical planning) to surgical guides and implants (**Figure 10**). The main advantages cited by the authors are reduced operating time, better medical outcomes, and reduced exposure to radiation [13–17].

## **19. Complications**

Arising from surgical extirpation of front ethmoidal sinus carcinoma depend on the approach and resection extent, ranging from wound infection to meningitis and death.

Extracranial approaches are associated with a low complication rate, most commonly wound infection and cerebrospinal fluid leakage. Intracranial resection is related to increased complications, such as meningitis and cerebrospinal fluid leakage, which have been the most frequently reported. The overall complication rate is less than 20%, with perioperative mortality in intracranial approaches between 0 and 13% [4–7, 9]. The rate of postoperative complications after preoperative radiation is significantly higher and ranges from 24–100% [9, 35]. Changes in mental status may result from significant frontal lobe resection. Outcomes of 5-year overall disease-specific survival rates for patients with malignant disease of paranasal sinuses range from 24 to 69% [4, 5]. Local recurrence is the leading cause of death in patients with malignant tumors, occurring in 38 to 89% of patients [7, 9, 35]. Radicality in tumor displacement is the most crucial point in treating tumors of this region, bearing in mind that it is often difficult for pathologists to determine resection margins. It should also be noted that more than 50% of patients with negative surgical margins experience local recurrence, probably due to difficulties in achieving wide *en bloc* resections and evaluating the resection margins at this location, primarily when the disease has spread to the skull base, adjacent ethmoid sinuses, and orbital walls. In comparison to patients with dural and orbital involvement, 5-year survival rates were higher in patients without the invasion of these structures (23–29% vs. 48–69%) [9, 35].

## **20. Conclusion**

Modern surgical treatment of extensive tumors in the frontoethmoidal region and anterior skull base shows satisfactory surgical results and good clinical outcomes. Modern microsurgical techniques, diagnostic imaging, preoperative analysis, and 3D technology have significantly changed the concept of tumors in this region. The

*Extensive Tumors of the Frontoethmoidal Region DOI: http://dx.doi.org/10.5772/intechopen.113298*

possibility of adequate proactive preparation of the anesthesiological surgical team, which is multidisciplinary, leads to a reduction of intraoperative and postoperative complications.

## **Acknowledgement**

I would like to thank Prof. Zlatibor Andjelković for his consent to use **Figure 4**.

## **Author details**

Dragan Krasic1,2\*, Stasa Krasic3 , Milos Trajkovic1 and Nebojsa Stojanovic2,4

1 Clinic for Maxillofacial Surgery, Nis, Serbia

2 Medical Faculty, University of Nis, Nis, Serbia

3 Mother and Child Health Institute of Serbia, Belgrade, Serbia

4 Clinic for Neurosurgery, Medical Faculty, University of Nis, Serbia

\*Address all correspondence to: drkrasic@yahoo.com

© 2024 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section 5
