Clinical Review & Education
Clinical Problem Solving | PATHOLOGY
A Rapidly Enlarging Maxillary Lesion Nathan Eivaz, BS; Vatsal Patel, MD; William O. Collins, MD
A
B
C
D
Figure. A and B, Computed tomographic scans of a heterogeneous mass in the left maxillary sinus. A, Noncontrast scan. B, Contrast-enhanced scan. C and D, Histopathologic images of biopsy specimen. C, Hematoxylin-eosin, original magnification ×20. D, Hematoxylin-eosin, original magnification ×10.
A teenage girl was seen at the emergency department after several months of sinus pressure and facial swelling and several weeks of external deviation of her nasal septum. On examination, a left nasal mass was noted. Computed tomographic (CT) scans without and with contrast showed a heterogeneous mass with solid and cystic components completely opacifying the left maxillary sinus (Figure, A and B, respectively). The mass eroded the orbital floor, medial and posterior maxillary walls, and anterior ethmoid air cells. There was no extension beyond the cribriform plate. Mild left-sided proptosis was noted, with displacement of the inferior rectus but no muscle invasion. The left maxillary alveolar ridge and several molar roots were involved. Bony changes were consistent with remodeling and thinning. Magnetic resonance imaging was unavailable because the patient had braces. Biopsy and tissue analysis demonstrated a spindle
jamaotolaryngology.com
cell process in a patternless arrangement with clinically significant multinucleated giant cells (Figure, C). The tissue specimen showed rare mitotic activity and lacked cytologic atypia. The mass was removed using a microdebrider and Tru-cut forceps. Curved olive-tip suction was placed between the maxillary sinus walls, nasal cavity, and anterior aspect of the mass. The tumor was collapsed in and removed in 5 portions; the largest measured 7.0 × 4.0 × 2.0 cm. The most firm, fibrotic portion of the tumor, centered on the posterior maxillary wall, was removed en bloc through identification of a fibrous dissection plane between the tumor and periosteum overlying the pterygopalatine space. At the 5-month follow-up the patient was stable and asymptomatic and showed no evidence of recurrence following excision and left maxillectomy. What is your diagnosis?
(Reprinted) JAMA Otolaryngology–Head & Neck Surgery March 2015 Volume 141, Number 3
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
287
Clinical Review & Education Clinical Problem Solving
Diagnosis Left maxillary giant cell reparative granuloma (GCRG)
Discussion Only 5% of pediatric tumors are primary head and neck masses; moreover, less than 1% originate in the nasal cavity or surrounding sinuses.1,2 Hemangioma and rhabdomyosarcoma represent the most common benign and malignant neoplasms, respectively.3 In this patient, rhabdomyosarcoma was the initial leading diagnosis based on the rapid course, CT images demonstrating a heterogeneous mass, and erosion through bony structures into the orbit and nasal cavity (Figure, B). However, histological examination of the tissue excluded rhabdomyosarcoma and more common entities, such as mucocele and solitary fibrous tumor. Consequently, the diagnosis was GCRG, a benign but occasionally aggressive and locally destructive entity. While the term granuloma indicates a reparative process, a history of overt trauma is not required in GCRG. Nonetheless, most of these lesions are presumed to occur after trauma. Inflammation is implicated in the pathophysiologic cause of these lesions in patients who have no history of trauma.4 Thus, chronic sinusitis may result in microhemorrhage and focal inflammation, triggering a reparative process. Despite such theories, a consensus on the etiology of GCRG remains elusive.5 Differential diagnosis of these lesions includes giant cell tumor, malignant fibrous histiocytoma, aneurysmal bone cyst, and resorptive giant cell granuloma associated with hyperparathyroidism (brown tumor). Histologic analysis is key in the tedious process of distinguishing GCRG from competing diagnoses of giant cell tumor and malignant fibrous histiocytoma. Brown tumors associated with hyperparathyroidism can be ruled out on the basis of laboratory testing. GCRG shows a background of proliferative, patternless spindled stroma and islands of microhemorrhage. Scattered throughout are multinucleated osteoclast-like giant cells (Figure, D). Sporadic bony spicules may also be found. It is the irregular distriARTICLE INFORMATION Author Affiliations: University of Florida College of Medicine, Gainesville (Eivaz); Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville (Patel); Department of Otolaryngology– Head and Neck Surgery, University of Florida College of Medicine, Gainesville (Collins). Corresponding Author: Nathan Eivaz, BS, University of Florida College of Medicine, 1700 SW 16th, Ct J4, Gainesville, FL 32608 ([email protected]). Section Editor: Edward B. Stelow, MD. Published Online: January 15, 2015. doi:10.1001/jamaoto.2014.3486. Conflict of Interest Disclosures: None reported. REFERENCES
bution of these giant cells throughout the specimen that distinguishes GCRG from giant cell tumor (GCT) among other things. Furthermore, GCT is a true neoplasm commonly found in the epiphysis of long bones during the third and fourth decades of life; such lesions are rarely found in the skull. Meanwhile, GCRG is mostly seen in the bones of the skull in 10- to 20-year-old female patients.5 The diagnosis of malignant fibrous histiocytoma (MFH) is multifactorial, because immunohistochemical analysis is unreliable. Both MFH and GCRG are negative when stained for actin, desmin, S100, and CD34. MFH is most frequently reported in older adults with propensity for the lower extremities. It rarely presents in the retroperitoneum and the head and neck region. A storiform “cartwheel-like” spindle cell background with scattered osteoclast-like giant cells is characteristic of MFH, but the presence of mitotic figures and cellular atypia distinguishes this lesion from GCRG.6 Aneurysmal bone cyst (ABC) and GCRG may have similar clinical presentation; they are occasionally and, controversially, regarded as the same entity. Moreover, a subset of GCRG carries the same mutation—a USP6 fusion gene rearrangement.7 ABC is common during the first 2 decades of life, targeting the vertebral column and metaphyseal long bones. Histologically, ABC is hemorrhagic and multicystic with frequent macroscopic thrombi. Blood-filled spaces are separated by fibrous septa containing bland, spindled fibroblasts and scattered osteoclast-like giant cells. Fibrous septa often undergo extensive calcification, colloquially referred to as “blue bone,” a distinctive and diagnostic characteristic.7 Whereas multinucleate giant cells are an abundant, defining feature of GCRG, they are sparsely scattered in ABC, occasionally absent entirely. Mitoses are commonly found, but cytologic atypia is absent.8 Although some variants of ABC and GCRG can look similar histologically, lack of large blood lakes with fibrous septa distinguishes the 2. Radiographically, ABC and GCRG may both appear expansile and lytic with a propensity to induce cortical thinning and a periosteal reaction; however, the many cysts and a prominent fluid level distinctively characterize ABC.7
2. Holsinger FC, Hafemeister AC, Hicks MJ, Sulek M, Huh WW, Friedman EM. Differential diagnosis of pediatric tumors of the nasal cavity and paranasal sinuses: a 45-year multi-institutional review. Ear Nose Throat J. 2010;89(11):534-540.
6. Okada H, Murai M, Yamamoto H. Malignant fibrous histiocytoma of the maxillary sinus: a case study of proliferative activity, immunohistochemistry, and electron microscopy. J Oral Maxillofac Surg. 1994;52(11):1193-1197.
3. Biswas D, Saha S, Bera SP. Relative distribution of the tumours of ear, nose and throat in the paediatric patients. Int J Pediatr Otorhinolaryngol. 2007;71(5):801-805.
7. Oliveira AM, Perez-Atayde AR, Inwards CY, et al. USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol. 2004;165(5):1773-1780.
4. Wiatrak BJ, Gluckman JL, Fabian RL, Wesseler TA. Giant cell reparative granuloma of the ethmoid sinus. Otolaryngol Head Neck Surg. 1987;97(5):504509.
8. Fletcher CD, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002:236-237.
5. Hirschl S, Katz A. Giant cell reparative granuloma outside the jaw bone: diagnostic criteria and review of the literature with the first case described in the temporal bone. Hum Pathol. 1974;5(2):171-181.
1. Cunningham MJ, Myers EN, Bluestone CD. Malignant tumors of the head and neck in children: a twenty-year review. Int J Pediatr Otorhinolaryngol. 1987;13(3):279-292.
288
JAMA Otolaryngology–Head & Neck Surgery March 2015 Volume 141, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
jamaotolaryngology.com
Clinical Problem Solving | PATHOLOGY
A Rapidly Enlarging Maxillary Lesion Nathan Eivaz, BS; Vatsal Patel, MD; William O. Collins, MD
A
B
C
D
Figure. A and B, Computed tomographic scans of a heterogeneous mass in the left maxillary sinus. A, Noncontrast scan. B, Contrast-enhanced scan. C and D, Histopathologic images of biopsy specimen. C, Hematoxylin-eosin, original magnification ×20. D, Hematoxylin-eosin, original magnification ×10.
A teenage girl was seen at the emergency department after several months of sinus pressure and facial swelling and several weeks of external deviation of her nasal septum. On examination, a left nasal mass was noted. Computed tomographic (CT) scans without and with contrast showed a heterogeneous mass with solid and cystic components completely opacifying the left maxillary sinus (Figure, A and B, respectively). The mass eroded the orbital floor, medial and posterior maxillary walls, and anterior ethmoid air cells. There was no extension beyond the cribriform plate. Mild left-sided proptosis was noted, with displacement of the inferior rectus but no muscle invasion. The left maxillary alveolar ridge and several molar roots were involved. Bony changes were consistent with remodeling and thinning. Magnetic resonance imaging was unavailable because the patient had braces. Biopsy and tissue analysis demonstrated a spindle
jamaotolaryngology.com
cell process in a patternless arrangement with clinically significant multinucleated giant cells (Figure, C). The tissue specimen showed rare mitotic activity and lacked cytologic atypia. The mass was removed using a microdebrider and Tru-cut forceps. Curved olive-tip suction was placed between the maxillary sinus walls, nasal cavity, and anterior aspect of the mass. The tumor was collapsed in and removed in 5 portions; the largest measured 7.0 × 4.0 × 2.0 cm. The most firm, fibrotic portion of the tumor, centered on the posterior maxillary wall, was removed en bloc through identification of a fibrous dissection plane between the tumor and periosteum overlying the pterygopalatine space. At the 5-month follow-up the patient was stable and asymptomatic and showed no evidence of recurrence following excision and left maxillectomy. What is your diagnosis?
(Reprinted) JAMA Otolaryngology–Head & Neck Surgery March 2015 Volume 141, Number 3
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
287
Clinical Review & Education Clinical Problem Solving
Diagnosis Left maxillary giant cell reparative granuloma (GCRG)
Discussion Only 5% of pediatric tumors are primary head and neck masses; moreover, less than 1% originate in the nasal cavity or surrounding sinuses.1,2 Hemangioma and rhabdomyosarcoma represent the most common benign and malignant neoplasms, respectively.3 In this patient, rhabdomyosarcoma was the initial leading diagnosis based on the rapid course, CT images demonstrating a heterogeneous mass, and erosion through bony structures into the orbit and nasal cavity (Figure, B). However, histological examination of the tissue excluded rhabdomyosarcoma and more common entities, such as mucocele and solitary fibrous tumor. Consequently, the diagnosis was GCRG, a benign but occasionally aggressive and locally destructive entity. While the term granuloma indicates a reparative process, a history of overt trauma is not required in GCRG. Nonetheless, most of these lesions are presumed to occur after trauma. Inflammation is implicated in the pathophysiologic cause of these lesions in patients who have no history of trauma.4 Thus, chronic sinusitis may result in microhemorrhage and focal inflammation, triggering a reparative process. Despite such theories, a consensus on the etiology of GCRG remains elusive.5 Differential diagnosis of these lesions includes giant cell tumor, malignant fibrous histiocytoma, aneurysmal bone cyst, and resorptive giant cell granuloma associated with hyperparathyroidism (brown tumor). Histologic analysis is key in the tedious process of distinguishing GCRG from competing diagnoses of giant cell tumor and malignant fibrous histiocytoma. Brown tumors associated with hyperparathyroidism can be ruled out on the basis of laboratory testing. GCRG shows a background of proliferative, patternless spindled stroma and islands of microhemorrhage. Scattered throughout are multinucleated osteoclast-like giant cells (Figure, D). Sporadic bony spicules may also be found. It is the irregular distriARTICLE INFORMATION Author Affiliations: University of Florida College of Medicine, Gainesville (Eivaz); Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville (Patel); Department of Otolaryngology– Head and Neck Surgery, University of Florida College of Medicine, Gainesville (Collins). Corresponding Author: Nathan Eivaz, BS, University of Florida College of Medicine, 1700 SW 16th, Ct J4, Gainesville, FL 32608 ([email protected]). Section Editor: Edward B. Stelow, MD. Published Online: January 15, 2015. doi:10.1001/jamaoto.2014.3486. Conflict of Interest Disclosures: None reported. REFERENCES
bution of these giant cells throughout the specimen that distinguishes GCRG from giant cell tumor (GCT) among other things. Furthermore, GCT is a true neoplasm commonly found in the epiphysis of long bones during the third and fourth decades of life; such lesions are rarely found in the skull. Meanwhile, GCRG is mostly seen in the bones of the skull in 10- to 20-year-old female patients.5 The diagnosis of malignant fibrous histiocytoma (MFH) is multifactorial, because immunohistochemical analysis is unreliable. Both MFH and GCRG are negative when stained for actin, desmin, S100, and CD34. MFH is most frequently reported in older adults with propensity for the lower extremities. It rarely presents in the retroperitoneum and the head and neck region. A storiform “cartwheel-like” spindle cell background with scattered osteoclast-like giant cells is characteristic of MFH, but the presence of mitotic figures and cellular atypia distinguishes this lesion from GCRG.6 Aneurysmal bone cyst (ABC) and GCRG may have similar clinical presentation; they are occasionally and, controversially, regarded as the same entity. Moreover, a subset of GCRG carries the same mutation—a USP6 fusion gene rearrangement.7 ABC is common during the first 2 decades of life, targeting the vertebral column and metaphyseal long bones. Histologically, ABC is hemorrhagic and multicystic with frequent macroscopic thrombi. Blood-filled spaces are separated by fibrous septa containing bland, spindled fibroblasts and scattered osteoclast-like giant cells. Fibrous septa often undergo extensive calcification, colloquially referred to as “blue bone,” a distinctive and diagnostic characteristic.7 Whereas multinucleate giant cells are an abundant, defining feature of GCRG, they are sparsely scattered in ABC, occasionally absent entirely. Mitoses are commonly found, but cytologic atypia is absent.8 Although some variants of ABC and GCRG can look similar histologically, lack of large blood lakes with fibrous septa distinguishes the 2. Radiographically, ABC and GCRG may both appear expansile and lytic with a propensity to induce cortical thinning and a periosteal reaction; however, the many cysts and a prominent fluid level distinctively characterize ABC.7
2. Holsinger FC, Hafemeister AC, Hicks MJ, Sulek M, Huh WW, Friedman EM. Differential diagnosis of pediatric tumors of the nasal cavity and paranasal sinuses: a 45-year multi-institutional review. Ear Nose Throat J. 2010;89(11):534-540.
6. Okada H, Murai M, Yamamoto H. Malignant fibrous histiocytoma of the maxillary sinus: a case study of proliferative activity, immunohistochemistry, and electron microscopy. J Oral Maxillofac Surg. 1994;52(11):1193-1197.
3. Biswas D, Saha S, Bera SP. Relative distribution of the tumours of ear, nose and throat in the paediatric patients. Int J Pediatr Otorhinolaryngol. 2007;71(5):801-805.
7. Oliveira AM, Perez-Atayde AR, Inwards CY, et al. USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol. 2004;165(5):1773-1780.
4. Wiatrak BJ, Gluckman JL, Fabian RL, Wesseler TA. Giant cell reparative granuloma of the ethmoid sinus. Otolaryngol Head Neck Surg. 1987;97(5):504509.
8. Fletcher CD, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002:236-237.
5. Hirschl S, Katz A. Giant cell reparative granuloma outside the jaw bone: diagnostic criteria and review of the literature with the first case described in the temporal bone. Hum Pathol. 1974;5(2):171-181.
1. Cunningham MJ, Myers EN, Bluestone CD. Malignant tumors of the head and neck in children: a twenty-year review. Int J Pediatr Otorhinolaryngol. 1987;13(3):279-292.
288
JAMA Otolaryngology–Head & Neck Surgery March 2015 Volume 141, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
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