Clinical Review & Education
Clinical Challenge | PATHOLOGY
An Infratemporal Fossa Mass Apoorva Tewari, BS; Jeffrey Blumberg, MD; Saral Mehra, MD
A
C
B
D
Figure. A, Coronal computed tomographic scan of the mass. B, Postcontrast axial T1-weighted magnetic resonance image. C, Gross pathologic image of the mass. D, Histopathologic image of excised tissue (hematoxylin-eosin, original magnification ×40).
A man in his 50s presented with a facial mass growing over 1 year, with 28.5-kg weight loss due to poor oral intake. He reported a 44–pack-year smoking history and remote alcohol abuse. On physical examination he had a 10-cm right-sided facial mass extending under the auricle from the mastoid to the zygoma and inferiorly to the angle of the mandible. The mass was firm, mildly tender, but without overlying skin changes or cervical lymphadenopathy. Computed toQuiz at mographic (CT) and magnetic resonance imaging (MRI) jamaotolaryngology.com scans showed maxillary sinus compression with partial destruction of the zygomatic arch, mandible, and orbital floor (Figure, A and B). The mass extended into the right pterygopalatine fossa, disrupting the floor of the middle cranial fossa and widening the foramen ovale. A core biopsy specimen revealed spindle cell proliferation with abundant collagen that stained focally with CD34, smooth muscle actin, and Bcl-2. The Figure, C, shows a gross pathologic image after excision of the mass.Histopathologic findings demonstrated spindle cells arranged in long fascicles with abundant interstitial collagen (Figure, D). Tumor cells exhibited central, oval nuclei, and moderate amounts of pale-pink cytoplasm with indistinct borders. There was no increased or atypical mitosis, necrosis, or vascular invasion. Immunostaining demonstrated strong nuclear staining for β-catenin antibody and was positive for smooth muscle actin antibody, while stains for desmin, pan-keratin, S-100, CD34, and Bcl-2 antibodies were negative. The Ki67 index was less than 1%.
jamaotolaryngology.com
WHAT IS YOUR DIAGNOSIS?
A. Pleomorphic adenoma B. Desmoid tumor C. Fibrosarcoma D. Rhabdomyosarcoma
(Reprinted) JAMA Otolaryngology–Head & Neck Surgery June 2015 Volume 141, Number 6
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 06/18/2015
575
Clinical Review & Education Clinical Challenge
Diagnosis B. Desmoid tumor
Discussion Desmoid tumors, also called aggressive fibromatoses, are rare, locally aggressive soft-tissue tumors that occur in 2 to 4 cases per million per year. They are categorized as benign neoplasms owing to their lack of mitotic activity or metastatic potential. However, some authors1 consider them malignant tumors owing to their aggressive behavior. The median age of affected patients is 37 years. 2 Presentation is largely due to mass effect and local destruction of organs. Most present in the abdomen and abdominal wall. Only 12% of desmoid tumors presents in the head and neck.3 Of these, most present at the base of the neck and perivertebral space.4 The etiology of desmoid tumors remains controversial. Some postulate that estrogen may be involved. Estrogen and progesterone receptors can be found in 30% of tumors. Some series demonstrate increased incidence in pregnant women, and case reports have also demonstrated women developing desmoid tumors after starting oral contraceptives.5 More recent series suggest there is no association with pregnancy and that this association is even less relevant for desmoid tumors of the head and neck. Traumatic history can be elicited in 25% of cases. However, this association is questionable because these are clonal disorders rather than reactive inflammatory proliferations.6 Desmoid tumors are associated with syndromes involving inactivating mutations in the APC gene, a tumor suppressor that negatively regulates the Wnt signaling pathway. These syndromes include familial adenomatous polyposis, hereditary desmoid disease, and familial infiltrative fibromatosis.7 However, most patients have sporadic tumors, which are associated with activating mutations in β-catenin, a positive regulator of the Wnt pathway.8 Imaging helps to determine the true size of these tumors and to evaluate local invasion into surrounding structures such as bone ARTICLE INFORMATION Author Affiliations: Department of Otolaryngology, Yale University, New Haven, Connecticut. Corresponding Author: Saral Mehra, MD, Department of Otolaryngology, Yale University, 789 Howard Ave, Dana Building, New Haven, CT 06519 ([email protected]). Section Editor: Edward B. Stelow, MD. Published Online: April 16, 2015. doi:10.1001/jamaoto.2015.0517. Conflict of Interest Disclosures: None reported. REFERENCES 1. Munch J. Desmoid tumors: multidisciplinary treatment for an enigmatic diseases. OncoLog Newsletter, M. D. Anderson Cancer Center. November-December 2010, Vol. 55(11-12). http: //www2.mdanderson.org/depts/oncolog/articles /10/11-12-novdec/11-12-10-1.html. Accessed March 16, 2015.
576
and the skull base in order to plan the resection.5 On CT scans they are isodense to hyperdense relative to muscle, and they do not enhance significantly with contrast.4 Although MRI has little value in determining margins, it is helpful in delineating relationships with neurovascular structures, particularly at the skull base.4 These lesions demonstrate wide variability in signal intensity on MRI, although most demonstrate marked enhancement on contrast-MRI along with nonenhancing bands, the latter of which are correlated with hypocellular areas with dense collagen stroma on histopathologic examination.4 These tumors cannot be distinguished from other soft-tissue tumors on imaging alone. The differential diagnosis of desmoid tumors of the head and neck includes solitary fibrous tumor, fibrosarcomas, leiomyomas, low-grade fibromyxoid sarcoma, neurofibroma, and schwannomas. Grossly, they are firm, fibrous, and often infiltrative into adjacent tissue. Although they may appear encapsulated, microscopic invasion often extends beyond the apparent capsule.5 Microscopically, they are characterized by spindle cells representing mesenchymal fibroblastic and myofibroblastic cells in a dense collagenous stroma. Desmoid tumors have less mitotic activity, smaller nucleus to cytoplasm ratio, and less vascularity than fibrosarcomas.5 Extra-abdominal desmoid tumors demonstrate nuclear translocation of β-catenin and stain positively for cathepsin D, actin, desmin, and vimentin.9,10 A minority stains positively for somatostatin, androgen receptor, estrogen receptor β, and Ki-67.10 The behavior of these tumors can vary from multiple local recurrences with local destruction, stability after a period of growth, and regression.2 Up to 40% to 60% of desmoids recur, mostly within 2 years of resection. However, rates of recurrence have decreased in the setting of postoperative radiation and systemic therapy.2 Potential medical therapies have limited benefits, but chemotherapy, antiestrogen medications, nonsteroidal anti-inflammatory drugs, and imatinib are options to consider. Younger age at presentation, larger tumor size, and extra-abdominal tumors are associated with poorer survival rates.2
2. Salas S, Dufresne A, Bui B, et al. Prognostic factors influencing progression-free survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation. J Clin Oncol. 2011;29(26):3553-3558.
8. Le Guellec S, Soubeyran I, Rochaix P, et al. CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics. Mod Pathol. 2012;25(12):1551-1558.
3. Masson JK, Soule EH. Desmoid tumors of the head and neck. Am J Surg. 1966;112(4):615-622.
9. Angiero F, Benedicenti S, Stefani M. Fibromatosis of the head and neck: morphological, immunohistochemical and clinical features. Anticancer Res. 2008;28(3B):1725-1732.
4. Rhim JH, Kim JH, Moon KC, et al. Desmoid-type fibromatosis in the head and neck: CT and MR imaging characteristics. Neuroradiology. 2013;55 (3):351-359. 5. Shields CJ, Winter DC, Kirwan WO, Redmond HP. Desmoid tumours. Eur J Surg Oncol. 2001;27(8): 701-706.
10. Leithner A, Gapp M, Radl R, et al. Immunohistochemical analysis of desmoid tumours. J Clin Pathol. 2005;58(11):1152-1156.
6. de Bree E, Zoras O, Hunt JL, et al. Desmoid tumors of the head and neck: a therapeutic challenge. Head Neck. 2014;36(10):1517-1526. 7. Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009;35(1):3-10.
JAMA Otolaryngology–Head & Neck Surgery June 2015 Volume 141, Number 6 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 06/18/2015
jamaotolaryngology.com
Clinical Challenge | PATHOLOGY
An Infratemporal Fossa Mass Apoorva Tewari, BS; Jeffrey Blumberg, MD; Saral Mehra, MD
A
C
B
D
Figure. A, Coronal computed tomographic scan of the mass. B, Postcontrast axial T1-weighted magnetic resonance image. C, Gross pathologic image of the mass. D, Histopathologic image of excised tissue (hematoxylin-eosin, original magnification ×40).
A man in his 50s presented with a facial mass growing over 1 year, with 28.5-kg weight loss due to poor oral intake. He reported a 44–pack-year smoking history and remote alcohol abuse. On physical examination he had a 10-cm right-sided facial mass extending under the auricle from the mastoid to the zygoma and inferiorly to the angle of the mandible. The mass was firm, mildly tender, but without overlying skin changes or cervical lymphadenopathy. Computed toQuiz at mographic (CT) and magnetic resonance imaging (MRI) jamaotolaryngology.com scans showed maxillary sinus compression with partial destruction of the zygomatic arch, mandible, and orbital floor (Figure, A and B). The mass extended into the right pterygopalatine fossa, disrupting the floor of the middle cranial fossa and widening the foramen ovale. A core biopsy specimen revealed spindle cell proliferation with abundant collagen that stained focally with CD34, smooth muscle actin, and Bcl-2. The Figure, C, shows a gross pathologic image after excision of the mass.Histopathologic findings demonstrated spindle cells arranged in long fascicles with abundant interstitial collagen (Figure, D). Tumor cells exhibited central, oval nuclei, and moderate amounts of pale-pink cytoplasm with indistinct borders. There was no increased or atypical mitosis, necrosis, or vascular invasion. Immunostaining demonstrated strong nuclear staining for β-catenin antibody and was positive for smooth muscle actin antibody, while stains for desmin, pan-keratin, S-100, CD34, and Bcl-2 antibodies were negative. The Ki67 index was less than 1%.
jamaotolaryngology.com
WHAT IS YOUR DIAGNOSIS?
A. Pleomorphic adenoma B. Desmoid tumor C. Fibrosarcoma D. Rhabdomyosarcoma
(Reprinted) JAMA Otolaryngology–Head & Neck Surgery June 2015 Volume 141, Number 6
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 06/18/2015
575
Clinical Review & Education Clinical Challenge
Diagnosis B. Desmoid tumor
Discussion Desmoid tumors, also called aggressive fibromatoses, are rare, locally aggressive soft-tissue tumors that occur in 2 to 4 cases per million per year. They are categorized as benign neoplasms owing to their lack of mitotic activity or metastatic potential. However, some authors1 consider them malignant tumors owing to their aggressive behavior. The median age of affected patients is 37 years. 2 Presentation is largely due to mass effect and local destruction of organs. Most present in the abdomen and abdominal wall. Only 12% of desmoid tumors presents in the head and neck.3 Of these, most present at the base of the neck and perivertebral space.4 The etiology of desmoid tumors remains controversial. Some postulate that estrogen may be involved. Estrogen and progesterone receptors can be found in 30% of tumors. Some series demonstrate increased incidence in pregnant women, and case reports have also demonstrated women developing desmoid tumors after starting oral contraceptives.5 More recent series suggest there is no association with pregnancy and that this association is even less relevant for desmoid tumors of the head and neck. Traumatic history can be elicited in 25% of cases. However, this association is questionable because these are clonal disorders rather than reactive inflammatory proliferations.6 Desmoid tumors are associated with syndromes involving inactivating mutations in the APC gene, a tumor suppressor that negatively regulates the Wnt signaling pathway. These syndromes include familial adenomatous polyposis, hereditary desmoid disease, and familial infiltrative fibromatosis.7 However, most patients have sporadic tumors, which are associated with activating mutations in β-catenin, a positive regulator of the Wnt pathway.8 Imaging helps to determine the true size of these tumors and to evaluate local invasion into surrounding structures such as bone ARTICLE INFORMATION Author Affiliations: Department of Otolaryngology, Yale University, New Haven, Connecticut. Corresponding Author: Saral Mehra, MD, Department of Otolaryngology, Yale University, 789 Howard Ave, Dana Building, New Haven, CT 06519 ([email protected]). Section Editor: Edward B. Stelow, MD. Published Online: April 16, 2015. doi:10.1001/jamaoto.2015.0517. Conflict of Interest Disclosures: None reported. REFERENCES 1. Munch J. Desmoid tumors: multidisciplinary treatment for an enigmatic diseases. OncoLog Newsletter, M. D. Anderson Cancer Center. November-December 2010, Vol. 55(11-12). http: //www2.mdanderson.org/depts/oncolog/articles /10/11-12-novdec/11-12-10-1.html. Accessed March 16, 2015.
576
and the skull base in order to plan the resection.5 On CT scans they are isodense to hyperdense relative to muscle, and they do not enhance significantly with contrast.4 Although MRI has little value in determining margins, it is helpful in delineating relationships with neurovascular structures, particularly at the skull base.4 These lesions demonstrate wide variability in signal intensity on MRI, although most demonstrate marked enhancement on contrast-MRI along with nonenhancing bands, the latter of which are correlated with hypocellular areas with dense collagen stroma on histopathologic examination.4 These tumors cannot be distinguished from other soft-tissue tumors on imaging alone. The differential diagnosis of desmoid tumors of the head and neck includes solitary fibrous tumor, fibrosarcomas, leiomyomas, low-grade fibromyxoid sarcoma, neurofibroma, and schwannomas. Grossly, they are firm, fibrous, and often infiltrative into adjacent tissue. Although they may appear encapsulated, microscopic invasion often extends beyond the apparent capsule.5 Microscopically, they are characterized by spindle cells representing mesenchymal fibroblastic and myofibroblastic cells in a dense collagenous stroma. Desmoid tumors have less mitotic activity, smaller nucleus to cytoplasm ratio, and less vascularity than fibrosarcomas.5 Extra-abdominal desmoid tumors demonstrate nuclear translocation of β-catenin and stain positively for cathepsin D, actin, desmin, and vimentin.9,10 A minority stains positively for somatostatin, androgen receptor, estrogen receptor β, and Ki-67.10 The behavior of these tumors can vary from multiple local recurrences with local destruction, stability after a period of growth, and regression.2 Up to 40% to 60% of desmoids recur, mostly within 2 years of resection. However, rates of recurrence have decreased in the setting of postoperative radiation and systemic therapy.2 Potential medical therapies have limited benefits, but chemotherapy, antiestrogen medications, nonsteroidal anti-inflammatory drugs, and imatinib are options to consider. Younger age at presentation, larger tumor size, and extra-abdominal tumors are associated with poorer survival rates.2
2. Salas S, Dufresne A, Bui B, et al. Prognostic factors influencing progression-free survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation. J Clin Oncol. 2011;29(26):3553-3558.
8. Le Guellec S, Soubeyran I, Rochaix P, et al. CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics. Mod Pathol. 2012;25(12):1551-1558.
3. Masson JK, Soule EH. Desmoid tumors of the head and neck. Am J Surg. 1966;112(4):615-622.
9. Angiero F, Benedicenti S, Stefani M. Fibromatosis of the head and neck: morphological, immunohistochemical and clinical features. Anticancer Res. 2008;28(3B):1725-1732.
4. Rhim JH, Kim JH, Moon KC, et al. Desmoid-type fibromatosis in the head and neck: CT and MR imaging characteristics. Neuroradiology. 2013;55 (3):351-359. 5. Shields CJ, Winter DC, Kirwan WO, Redmond HP. Desmoid tumours. Eur J Surg Oncol. 2001;27(8): 701-706.
10. Leithner A, Gapp M, Radl R, et al. Immunohistochemical analysis of desmoid tumours. J Clin Pathol. 2005;58(11):1152-1156.
6. de Bree E, Zoras O, Hunt JL, et al. Desmoid tumors of the head and neck: a therapeutic challenge. Head Neck. 2014;36(10):1517-1526. 7. Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009;35(1):3-10.
JAMA Otolaryngology–Head & Neck Surgery June 2015 Volume 141, Number 6 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 06/18/2015
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