- Email: [email protected]
Familiar and unfamiliar pseudoneoplastic lesions of the head and neck
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Available online at www.sciencedirect.com
www.elsevier.com/locate/semdp
Familiar and unfamiliar pseudoneoplastic lesions of the head and neck Mary S. Richardson, MD, DDS Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Ave, MSC 908, Charleston, South Carolina 29425-9080
article info
abstract
Keywords:
Pseudoneoplastic lesions in the head and neck are numerous. Familiarity with the sites of
Pseudoneoplasms
predilection and demographics of these lesions is particularly useful if the differential
hamartoma
diagnosis for a minimal biopsy sample includes benign and malignant entities. This article
Juxtaoral organ of Chievitz
is a brief overview of some common and unusual pseudo neoplasms specific to this region.
Eosinophilic angiocentric fibrosis
Introduction A number of lesions that occur in the head and neck may simulate malignancy if only a single perspective of radiographic or clinical or pathologic examination is used to assess the lesion. A multidisciplinary approach, in some situations, will be vital to integrating information that enables the correct assessment of the process. The purpose of this article is to provide a brief overview of a narrow set of challenging and unusual entities, some unique to the head and neck region. These entities may be encountered by a surgical pathology service in a variety of settings including at the time of intraoperative consultation. The topics discussed will include selected malignant mimics (pseudoneoplastic lesions) from the oral cavity, salivary gland tissue, sinonasal tract and larynx. Biologically these entities represent a broad spectrum of lesions from normal structures to entities with a yet undefined or uncertain classification.
Pseudoneoplasms of the oral cavity Juxtaoral organ of Chievitz The juxtaoral organ of Chievitz (JOOC) is composed of intermingled epithelial parenchyma and mesenchymal E-mail address: [email protected] http://dx.doi.org/10.1053/j.semdp.2015.09.004 0740-2570/& 2016 Published by Elsevier Inc.
& 2016 Published by Elsevier Inc.
components, which persist throughout life. This normal anatomic structure can be located within the connected tissue between the medial aspect of the mandible and the buccinator muscle near the angle of the mandible (retro molar trigone and ascending ramus). The organ function is thought to be as a mechanosensor, similar to the Pacinian corpuscle. The JOOC is seen intimately associated with a rich bed of nerves and is usually innervated by the branches of the buccal nerve.1 The epithelium of the JOOC is most often composed of squamous epithelium devoid of keratin formation, although columnar glandular-like cells with clear cytoplasm and luminal secretions have also been described. The basal layer of cells in the circumscribed islands often exhibit peripheral palisading and are usually devoid of mitotic figures (Fig. 1). Rarely has dystrophic calcification been associated with the nests.2 The epithelial nests can be seen in an intraneural or perineural location. Awareness of this normal structure, its histomorphology, anatomic location, and intimate association with nerves is key to prevent a misinterpretation of JOOC as invasive squamous carcinoma with perineural invasion, peripheral ameloblastoma, or mucoepidermoid carcinoma. This is a caveat for the pathologist as a pseudoneoplasm; there is no clinical or radiologic corollary for this entity. Small biopsies, resection margins or frozen section margins with artifactual change could easily
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Fig. 1 – This juxtaoral organ of Chievitz exhibits epithelial nests and islands adjacent to a neurovascular bed. The nests show peripheral palisading, with vague reverse polarization of the basal layer. No mitotic figure are seen (H&E; original magnification, 200 ). be over diagnosed as invasive carcinoma or perineural invasion. If the anatomic location of the procured tissue is provided or requested then certainly the JOOC structure could be appropriately considered during the histologic examination. Diagnostic errors of JOOC could result in significant misdirected patient treatment. Pathology arising from the JOOC is very uncommon. Rare cases describing a mass have been reported in an adult and children but no carcinomas to date have been attributed to this organ.3,4
Pseudoepitheliomatous hyperplasia Pseudoepitheliomatous hyperplasia (PEH) is a reactive, nonneoplastic proliferation of mucosal surface epithelium. The proliferation creates markedly elongated rete ridges that resemble the low-power microscopic architecture of invasive squamous cell carcinoma. The prominent downward growth of the surface epithelium, coupled with abrupt focal keratinization, may make the distinction from squamous cell carcinoma very challenging or impossible, especially without subjacent connective tissue for further assessment. Often the lateral extent of this lesion is sharply defined prompting
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investigation for the nidus of the marked epithelial proliferation (Fig. 2). This reactive proliferation is frequently observed at the edges of chronic nonspecific ulcers seen in the head and neck, particularly within the oral cavity and in the larynx following intubation. PEH can be seen in association with inflammatory processes such as inflammatory papillary hyperplasia beneath a dental prosthesis or obturator, associated with fungal infections such as blastomycosis, observed at the edges of discoid lupus erythematosus and has been associated with granular cell tumors.5–7 The example of PEH associated with a granular cell tumor is notoriously difficult when examining a small superficial or shallow biopsy (Fig. 2). The more common intraoral sites with a predilection for granular cell tumors are tongue (usually dorsal surface), buccal mucosa and floor of mouth. Another site of predilection within the head and neck is the larynx, in particular, the true vocal cord, a location where small and shallow biopsies are frequent. Again the importance of the anatomic location of the biopsy and knowledge about patterns of distribution of the disease process are imperative for eliminating possibilities within a differential diagnosis.
Eosinophilic ulceration Events of trauma to the oral mucosa may result in surface ulceration. The tongue, buccal mucosa, and floor of mouth are common sites for trauma from mastication, iatrogenic events, and idiopathic causes. The duration required for healing may vary from a few days to weeks. Eosinophilic ulceration (EU) [Traumatic granuloma, Traumatic ulcerative granuloma with stromal is eosinophilia (TUGSE)], is an exuberant pseudo invasive inflammatory reaction which is slow to heal. Reported delays in healing for EU have been as long as 8 months.8 The extended healing phase often causes concern for a neoplastic process, prompting a biopsy. Microscopically, this lesion is characterized by granulation tissue composed of plump endothelial cells with an associated dense inflammatory infiltrate; often seen extending deeply into connective tissue and splaying skeletal muscle (Fig. 3). The inflammatory infiltrate is composed primarily of histiocytes, activated lymphocytes, neutrophils and eosinophils, sometimes prompting concern for a lymphoproliferative
Fig. 2 – The lower architecture suggests the possibility of an invasive epitheil malignancy with the marked downward growth and fragmented islands. The transition from normal to proliferating epithelium is abrupt. The high power examination of the advancing epithelial front shows the presence of the subjacent granular cell tumor and the diagnosis of PEH is possible (H&E; original magnifications, 40 and 200 ).
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Fig. 3 – The source of traumatic injury is identified for this chronic ulcerated lesion on the ventral surface of the tongue. Microscopically numerous eosinophils, lymphocytes and granulation tissue are noted splaying skeletal muscle fibers. (Clinical photo courtesy of Dr. Brad Neviile MUSC School of Dental Medicine; H&E; original magnification, 200 .) disorder. CD30þ positive cells have been reported in some cases, although their exact significance is unresolved.9 Interestingly, often EU resolves promptly after an incisional biopsy; however, it would resolve spontaneously without surgical intervention.
Central giant cell granuloma (giant cell lesion) Central giant cell granuloma (CGCG) is an intraosseous lesion and has an unknown etiology with variable clinical patterns (aggressive and non-aggressive). The lesion is relatively uncommon, although it raises the consideration of a myriad of entities associated with giant cell formations within the craniofacial bones (aneurysmal bone cyst, osteitis fibrosa cystica, numerous benign fibro osseous lesions, including cherubism) necessitating clinicoradiologic correlation to achieve the appropriate diagnosis. Central giant cell granuloma (CGCG) is a variably aggressive lesion with the nonaggressive form having a slow rate of expansile growth, less likely to perforate cortical bone and low recurrence rate in comparison to the aggressive form. In contrast to giant cell tumors of long bones, CGCG is less aggressive, occurs in a younger age group (below 30 years of age) and have a female predilection. Radiographically the lesions of CGCG can be
Fig. 4 – This biopsy of a central giant cell granuloma from a 16 year old female, would be indistinguishable from other giant cell-associated lesions without the appropriate radiology and clinical workup (H&E; original magnification, 200 ).
unilocular or multilocular varying in size up to about 10 cm and occur more often in the mandible (anterior to the first molars crossing the midline) than maxilla.10,11 Histopathologically, central giant cell granuloma is identical to any other giant cell-associated osseous lesions in this region such as “brown tumor” of hyperparathyroidism (osteitis fibrosa cystica), as well as the multifocal giant cell lesions of heritable conditions such as cherubism. The tumor is composed of focal arrangements of multinucleated giant cells within a spindled and vascular stroma (Fig. 4). The radiographic distribution of lesions, clinical presentation and evaluation of the endocrine status of the patient need to be correlated to finalize a diagnosis. Surgery is the traditional treatment for CGCG with the extent ranging from curettage to en bloc resection. Recurrence of CGCG is not uncommon and has been reported to occur in approximately 45% of cases. The clinical features of those patients with an aggressive lesion may experience rapid growth and frequent recurrences prompting concern for a malignant process.11
Hyperplastic tooth follicle and dental papilla The tooth follicle (TF) and dental papilla (DP) (pulp) are normal components of odontogenesis. The tooth follicle is a connective tissue component that encases the developing tooth and is composed of collagenous fibers tissue with an intermingled myxomatous component. Contained within the wall of the tooth follicle are small inactive odontogenic epithelial remnants and frequently microcalcifications. The dental papilla is a myxomatous triangular or star shaped structure associated with immature unerupted teeth (Fig. 5). TF and DP may be present within the tooth bearing areas of the jaws and may extend into the maxillary sinus. Lack of familiarly with these innocuous normal structures poses a risk for misdiagnosing them as myxoma or possibly an odontogenic tumor, which could lead to unnecessary surgical procedures.5,12,13 Radiographic assessment should aid in deciphering whether the structures are either normal or represent the possibility of a myxoma or odontogenic tumor. These structures are usually encountered in specimens from third molar extractions or gnathic bone resections containing unerupted teeth. The clinicoradiologic information provided by the submitting surgeon, as well as the clinical assessment
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Fig. 5 – Tooth follicle is composed of collagenous connective tissue with scattered myxoid change and epithelial remnants. The epithelium may be surround by a hyaline like change in the immediate adjacent connective tissue.The dental papilla is composed of myxoid stroma and may be lined by remnants of odontoblasts. (H&E; original magnification, 100 ). of unerupted teeth with an associated “cyst,” should aid in the distinction.
Pseudoneoplasms of salivary gland tissue Necrotizing sialometaplasia A number of different lesions can present as a pseudoneoplasm of salivary gland tissues. However, the one lesion with the greatest possibility of being misdiagnosed as a malignant neoplasm is necrotizing sialometaplasia (NSM).14,15 This uncommon condition affects primarily minor salivary gland tissues or seromucous glands located throughout mucosal surfaces of the head and neck. NSM can occur in any site
containing minor seromucous glands such as the larynx and sinonasal tract but is most frequently seen in the palate.16,17 The key histologic features of the process are lobular mucus acinar necrosis and accompanying proliferative squamous metaplasia of the remaining lobular duct system of the seromucous unit affected. Clinically, the resulting finding is a crater-like depression, with or without associated ulceration, and markedly delayed healing of the clinical lesion. The lesion is usually asymptomatic and may or may not be associated with an inciting traumatic event. Microscopic examination shows partial necrosis of mucinous acini within their lobular arrangement (Fig. 6). Squamous metaplasia of the ducts may show reactivate atypia; however, the proliferation remains within the confines of the minor gland tissue perimeter. Depending on the orientation and depth of the
Fig. 6 – The loss of seromucous acini is striking in both examples of NSM, respiratory mucosa and palate. The squamous metaplasia is prominent in the remaining ducts and retains a lobular arrangement. These key features are easy to assess in an adequate biopsy of the process (H&E; original magnification, 100 ).
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Fig. 7 – The late phase of EAF shows extensive fibrosis. A low-power review shows loss of the normal architectural structure in this nasal mucosa biopsy. The whorled “onion skinning” fibrosis and arterioles with scattered stromal inflammatory cells and eosinophils is readily identifed at higher power examination (H&E; original magnifications, 40 and 200 ).
incisional biopsy, the histologic assessment may be adequate. Lack of atypical mitotic features and the retention of lobular architecture are the key features to a correct diagnosis.
Pseudoneoplasms of sinonasal tract and larynx
positive plasma cell infiltrate. There is no overt evidence of obliterative vasculitis in EAF, a finding that is prominent in other IgG4-related diseases.19 The predominance of the eosinophil infiltrate is noted throughout all phases of the disease. The prognosis of sinonasal EAF is indolent progressive clinical course. The primary mode of management is surgical; however, there are reported responses to immunotherapy.19
Eosinophilic angiocentric fibrosis
Sinonasal hamartomas Eosinophilic angiocentric fibrosis (EAF) is an enigmatic disease that can affect the nasal cavity, lacrimal glands, nasal sinuses, larynx, and lower respiratory track. Sinonasal EAF is an uncommon tumefactive lesion which mimics a neoplastic disorder. This condition is currently considered to be in the spectrum of the IgG4-related systemic diseases.18,19 The histology of the late phase of EAS is composed of small caliber arterioles surrounded by concentric layers of fibrosis “onion skinning.” The inflammatory cells are lymphoplasmacytic with a prominent eosinophil cell component. The histology of the early phase of EAF differs from the later phase. The inflammatory cells predominate in the early phase with progressive increase in the whorling fibrosis around arterioles (Fig. 7). Staining for IgG4 for plasma cells will demonstrate their presence within a background of IgG
Respiratory epithelial adenomatoid hamartoma The vast majority of sinonasal tract hamartomas are pure epithelial types, although pure mesenchymal types exist as well as mixed types. On clinical or radiological examination, these lesions may present is a polypoid mass usually without aggressive destruction of bone. Among the pure epithelial type hamartomas that may be encountered in sinonasal biopsy specimens is respiratory epithelial adenomatoid hamartoma (REAH). This lesion is most often noted in specimens from male patients with a polypoid mass located in the posterior nasal cavity or inferior turbinate, ethmoid, and maxillary sinuses. Since the original description of REAH in 1995, other associated features such as seromucus
Fig. 8 – This polypoid fragment of REAH illustrates the continium of the surface lining with the subepithelial hamartomatous lesion. The ductal structures are lined by a goblet cell-like mucous epithelium with cilia and are surrounded by a thickened basement membrane (H&E; original magnifications, 40 and 200 ).
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Fig. 9 – Lobulated growth of chondroid matrix within a mesenchymal like spindled stroma characterizes the NCMH (H&E; original magnification, 200 ).
hamartoma have been described. Histologically, REAH is composed of dilated small to medium caliber glands lined by ciliated respiratory epithelium, which often have a continuation with the surface epithelium. The glands are surrounded by a thickened eosinophilic basement membrane (Fig. 8). The possibility of progression and/or association of REAH, and glandular hamartomas with low-grade sinonasal adenocarcinomas is yet to be completely characterized.20-22 REAH lesion is currently best classified as inflammatoryrelated lesion.23
Mesenchymal hamartoma Nasal masses in children and young adults are infrequently encountered. Most nasal masses represent developmental anomalies such as encephalocele, nasal gliomas, nasolacrimal duct cyst and some hamartomatous lesions.24,25 There is a rare and benign lesion known as nasal chondromesenchymal hamartoma (NCMH) that occurs within the cranial facial bones, usually sinonasal region. The lesion may also be present as a congenital mass. The common clinical differential diagnosis for this lesion includes sarcoma or meningoencephalocele. The characteristic histologic features are a mixed stromal with chondroid tissue with a lobulated growth pattern (Fig. 9). The lesion is reminiscent of mesenchymal hamartoma of the chest wall. Interestingly, there has been a recent reporting of this lesion being associated with germline and somatic mutations of DICER 1.26 Management for this lesion is complete excision of the mass. At this point there is no known malignant transformation within these lesions and rarely do they recur when completely excised.
re fe r en ces
1. Pantanowtiz L, Balogh K. Significance of the juxtaoral organ (of Chevitz). Head Neck. 2003;25(5):400–405. 2. Sancheti SM, Sawaimoon S, Zameer MA. Juxtaoral organ of Chievitz, an obscure anatomical structure masquerading as perineural invasion of mucoepidermoid carcinoma: case report and review of literature. Int J Surg Pathol. 2015;23(6):461–463. 3. Ide F, Mishima K, Saito I. Juxtaoral organ of Chievitz presenting clinically as a tumour. J Clin Pathol. 2003;56(10):789–790.
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4. Soucy P, Climone G, Carpenter B. An unusual intraoral mass in a child: the organ of Chevitz. J Ped Surg. 1990;25(11): 1200. 5. El-Mofty SK. Pseudoneoplastic lesions of the head and neck. In: Wick MR, Humphrey PA, Ritter JH, eds. Pathology of Pseudoneoplastic lesions. Philadelphia: Lippincott-Ravin; 1997: 69–96. 6. Hanson JM, Spector G, El-Mofty SK. Laryngeal blastomycosis: a commonly missed diagnosis. Report of two cases and review of the literature. Ann Otol Rhinol Laryngol. 2000;109(3): 281–286. 7. Stewart CM, Watson RE, Eversole LR, Fischlschweiger W, Leider AS. Oral granular cell tumors: a clinicopathologic and immunohistochemical study. Oral Surg Oral Med Oral Pathol. 1988;65(4):427–435. 8. Neville BW, Damm DD, Allen CM, Chi AC, eds. Oral and Maxillofacial Pathology, 4th ed. St Louis: Elsevier Co. 2016: 260–262. 9. Salisbury CL, Budnick SD, Li S. T-cell receptor gene rearrangement and CD30 immunoreactivity in traumatic ulcerative granuloma with stromal eosinophilia of the oral cavity. Am J Clin Pathol. 2009;132(5):722–727. 10. Kaplan I, Manor I, Yahalom R, Hirshberg A. Central giant cell granuloma associated with central ossifying fibroma of the jaws: a clinicopathologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(4):e35–e41. 11. Kruse-Losler B, Diallo R, Gaertner C, Mischke K-L, Joos U, Kleinheinz J. Central giant cell granuloma of the jaws: a clinical, radiologic, and histopathologic study of 26 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3): 346–354. 12. Kim J, Ellis GL. Dental follicular tissue: misinterpretation as odontogenic tumors. J Oral Maxillofac Surg. 1993;51(7): 762–767. 13. Gardner DG, Radden B. Multiple calcifying hyperplastic dental follicles. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;79(5):603–606. 14. Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia. A disease stimulating malignancy. Cancer. 1973;32 (1):130–135. 15. Brannon RB, Fowler CB, Hartman KS. Necrotizing sialometaplasia. A clinicopathologic study of sixty-nine cases and review of the literature. Oral Surg Oral Med Oral Pathol. 1991;72(3):317–325. 16. Walker GK, Fechner RE, Johns ME, Teja K. Necrotizing sialometaplasia of the larynx secondary to atheromatous embolization. Am J Clin Pathol. 1982;77(2):221–223. 17. Wenig BM. Necrotizing sialometaplasia of the larynx. A report of two cases and a review of the literature. Am J Clin Pathol. 1995;103(5):609–613. 18. Deshpande V, Khosroshahi A, Nielsen GP, Hamilos DL, Stone JH. Eosinophilic angiocentric fibrosis is a form of IgG4-related systemic disease. Am J Surg Pathol. 2011;35(5):701–706. 19. Deshpande V. IgG4 related disease of the head and neck. Head Neck Pathol. 2015;9:24–31. 20. Jo Vy, Mills SE, Cathro HP, Carlson DL, Stelow EB. Low grade sinonasal adenocarcinomas: the association with and distinction from respiratory epithelial adenomatoid hamartomas and other glandular lesions. Am J Surg Pathol. 2009;33 (3):401–408. 21. Perez-Ordonez B. Hamartomas, papillomas and adenocarcinomas of the sinonasal tract and nasopharynx. J Clin Pathol. 2009;62:1085–1095. 22. Weinreb I. Low grade glandular lesions of the sinonasal tract: a focused review. Head Neck Pathol. 2010;4(1):77–83. 23. Wenig BM. Recently described sinonasal tract lesions/neoplasms: consideration for the new World Health Organization book. Head Neck Pathol. 2014;8(1):33–41.
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24. Ozolek JA, Carrau R, Barnes L, Hunt JL. Nasal chondromesenchymal hamartoma in older children and adults. Arch Pathol Lab Med. 2005;129:1444–1450. 25. Chandra M, Sharma N, Venkatachalam VP. Nasal chondromesenchymal hamartoma: a case report and review of literature. JK-Practitioner. 2014;19(1-2):53–59.
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26. Stewart DR, Messinger Y, Williams GM, et al. Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor-predisposition disorder. Hum Genet. 2014;133 (1):1443–1450.
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Available online at www.sciencedirect.com
www.elsevier.com/locate/semdp
Familiar and unfamiliar pseudoneoplastic lesions of the head and neck Mary S. Richardson, MD, DDS Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Ave, MSC 908, Charleston, South Carolina 29425-9080
article info
abstract
Keywords:
Pseudoneoplastic lesions in the head and neck are numerous. Familiarity with the sites of
Pseudoneoplasms
predilection and demographics of these lesions is particularly useful if the differential
hamartoma
diagnosis for a minimal biopsy sample includes benign and malignant entities. This article
Juxtaoral organ of Chievitz
is a brief overview of some common and unusual pseudo neoplasms specific to this region.
Eosinophilic angiocentric fibrosis
Introduction A number of lesions that occur in the head and neck may simulate malignancy if only a single perspective of radiographic or clinical or pathologic examination is used to assess the lesion. A multidisciplinary approach, in some situations, will be vital to integrating information that enables the correct assessment of the process. The purpose of this article is to provide a brief overview of a narrow set of challenging and unusual entities, some unique to the head and neck region. These entities may be encountered by a surgical pathology service in a variety of settings including at the time of intraoperative consultation. The topics discussed will include selected malignant mimics (pseudoneoplastic lesions) from the oral cavity, salivary gland tissue, sinonasal tract and larynx. Biologically these entities represent a broad spectrum of lesions from normal structures to entities with a yet undefined or uncertain classification.
Pseudoneoplasms of the oral cavity Juxtaoral organ of Chievitz The juxtaoral organ of Chievitz (JOOC) is composed of intermingled epithelial parenchyma and mesenchymal E-mail address: [email protected] http://dx.doi.org/10.1053/j.semdp.2015.09.004 0740-2570/& 2016 Published by Elsevier Inc.
& 2016 Published by Elsevier Inc.
components, which persist throughout life. This normal anatomic structure can be located within the connected tissue between the medial aspect of the mandible and the buccinator muscle near the angle of the mandible (retro molar trigone and ascending ramus). The organ function is thought to be as a mechanosensor, similar to the Pacinian corpuscle. The JOOC is seen intimately associated with a rich bed of nerves and is usually innervated by the branches of the buccal nerve.1 The epithelium of the JOOC is most often composed of squamous epithelium devoid of keratin formation, although columnar glandular-like cells with clear cytoplasm and luminal secretions have also been described. The basal layer of cells in the circumscribed islands often exhibit peripheral palisading and are usually devoid of mitotic figures (Fig. 1). Rarely has dystrophic calcification been associated with the nests.2 The epithelial nests can be seen in an intraneural or perineural location. Awareness of this normal structure, its histomorphology, anatomic location, and intimate association with nerves is key to prevent a misinterpretation of JOOC as invasive squamous carcinoma with perineural invasion, peripheral ameloblastoma, or mucoepidermoid carcinoma. This is a caveat for the pathologist as a pseudoneoplasm; there is no clinical or radiologic corollary for this entity. Small biopsies, resection margins or frozen section margins with artifactual change could easily
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Fig. 1 – This juxtaoral organ of Chievitz exhibits epithelial nests and islands adjacent to a neurovascular bed. The nests show peripheral palisading, with vague reverse polarization of the basal layer. No mitotic figure are seen (H&E; original magnification, 200 ). be over diagnosed as invasive carcinoma or perineural invasion. If the anatomic location of the procured tissue is provided or requested then certainly the JOOC structure could be appropriately considered during the histologic examination. Diagnostic errors of JOOC could result in significant misdirected patient treatment. Pathology arising from the JOOC is very uncommon. Rare cases describing a mass have been reported in an adult and children but no carcinomas to date have been attributed to this organ.3,4
Pseudoepitheliomatous hyperplasia Pseudoepitheliomatous hyperplasia (PEH) is a reactive, nonneoplastic proliferation of mucosal surface epithelium. The proliferation creates markedly elongated rete ridges that resemble the low-power microscopic architecture of invasive squamous cell carcinoma. The prominent downward growth of the surface epithelium, coupled with abrupt focal keratinization, may make the distinction from squamous cell carcinoma very challenging or impossible, especially without subjacent connective tissue for further assessment. Often the lateral extent of this lesion is sharply defined prompting
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33 (2016) 24–30
25
investigation for the nidus of the marked epithelial proliferation (Fig. 2). This reactive proliferation is frequently observed at the edges of chronic nonspecific ulcers seen in the head and neck, particularly within the oral cavity and in the larynx following intubation. PEH can be seen in association with inflammatory processes such as inflammatory papillary hyperplasia beneath a dental prosthesis or obturator, associated with fungal infections such as blastomycosis, observed at the edges of discoid lupus erythematosus and has been associated with granular cell tumors.5–7 The example of PEH associated with a granular cell tumor is notoriously difficult when examining a small superficial or shallow biopsy (Fig. 2). The more common intraoral sites with a predilection for granular cell tumors are tongue (usually dorsal surface), buccal mucosa and floor of mouth. Another site of predilection within the head and neck is the larynx, in particular, the true vocal cord, a location where small and shallow biopsies are frequent. Again the importance of the anatomic location of the biopsy and knowledge about patterns of distribution of the disease process are imperative for eliminating possibilities within a differential diagnosis.
Eosinophilic ulceration Events of trauma to the oral mucosa may result in surface ulceration. The tongue, buccal mucosa, and floor of mouth are common sites for trauma from mastication, iatrogenic events, and idiopathic causes. The duration required for healing may vary from a few days to weeks. Eosinophilic ulceration (EU) [Traumatic granuloma, Traumatic ulcerative granuloma with stromal is eosinophilia (TUGSE)], is an exuberant pseudo invasive inflammatory reaction which is slow to heal. Reported delays in healing for EU have been as long as 8 months.8 The extended healing phase often causes concern for a neoplastic process, prompting a biopsy. Microscopically, this lesion is characterized by granulation tissue composed of plump endothelial cells with an associated dense inflammatory infiltrate; often seen extending deeply into connective tissue and splaying skeletal muscle (Fig. 3). The inflammatory infiltrate is composed primarily of histiocytes, activated lymphocytes, neutrophils and eosinophils, sometimes prompting concern for a lymphoproliferative
Fig. 2 – The lower architecture suggests the possibility of an invasive epitheil malignancy with the marked downward growth and fragmented islands. The transition from normal to proliferating epithelium is abrupt. The high power examination of the advancing epithelial front shows the presence of the subjacent granular cell tumor and the diagnosis of PEH is possible (H&E; original magnifications, 40 and 200 ).
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Fig. 3 – The source of traumatic injury is identified for this chronic ulcerated lesion on the ventral surface of the tongue. Microscopically numerous eosinophils, lymphocytes and granulation tissue are noted splaying skeletal muscle fibers. (Clinical photo courtesy of Dr. Brad Neviile MUSC School of Dental Medicine; H&E; original magnification, 200 .) disorder. CD30þ positive cells have been reported in some cases, although their exact significance is unresolved.9 Interestingly, often EU resolves promptly after an incisional biopsy; however, it would resolve spontaneously without surgical intervention.
Central giant cell granuloma (giant cell lesion) Central giant cell granuloma (CGCG) is an intraosseous lesion and has an unknown etiology with variable clinical patterns (aggressive and non-aggressive). The lesion is relatively uncommon, although it raises the consideration of a myriad of entities associated with giant cell formations within the craniofacial bones (aneurysmal bone cyst, osteitis fibrosa cystica, numerous benign fibro osseous lesions, including cherubism) necessitating clinicoradiologic correlation to achieve the appropriate diagnosis. Central giant cell granuloma (CGCG) is a variably aggressive lesion with the nonaggressive form having a slow rate of expansile growth, less likely to perforate cortical bone and low recurrence rate in comparison to the aggressive form. In contrast to giant cell tumors of long bones, CGCG is less aggressive, occurs in a younger age group (below 30 years of age) and have a female predilection. Radiographically the lesions of CGCG can be
Fig. 4 – This biopsy of a central giant cell granuloma from a 16 year old female, would be indistinguishable from other giant cell-associated lesions without the appropriate radiology and clinical workup (H&E; original magnification, 200 ).
unilocular or multilocular varying in size up to about 10 cm and occur more often in the mandible (anterior to the first molars crossing the midline) than maxilla.10,11 Histopathologically, central giant cell granuloma is identical to any other giant cell-associated osseous lesions in this region such as “brown tumor” of hyperparathyroidism (osteitis fibrosa cystica), as well as the multifocal giant cell lesions of heritable conditions such as cherubism. The tumor is composed of focal arrangements of multinucleated giant cells within a spindled and vascular stroma (Fig. 4). The radiographic distribution of lesions, clinical presentation and evaluation of the endocrine status of the patient need to be correlated to finalize a diagnosis. Surgery is the traditional treatment for CGCG with the extent ranging from curettage to en bloc resection. Recurrence of CGCG is not uncommon and has been reported to occur in approximately 45% of cases. The clinical features of those patients with an aggressive lesion may experience rapid growth and frequent recurrences prompting concern for a malignant process.11
Hyperplastic tooth follicle and dental papilla The tooth follicle (TF) and dental papilla (DP) (pulp) are normal components of odontogenesis. The tooth follicle is a connective tissue component that encases the developing tooth and is composed of collagenous fibers tissue with an intermingled myxomatous component. Contained within the wall of the tooth follicle are small inactive odontogenic epithelial remnants and frequently microcalcifications. The dental papilla is a myxomatous triangular or star shaped structure associated with immature unerupted teeth (Fig. 5). TF and DP may be present within the tooth bearing areas of the jaws and may extend into the maxillary sinus. Lack of familiarly with these innocuous normal structures poses a risk for misdiagnosing them as myxoma or possibly an odontogenic tumor, which could lead to unnecessary surgical procedures.5,12,13 Radiographic assessment should aid in deciphering whether the structures are either normal or represent the possibility of a myxoma or odontogenic tumor. These structures are usually encountered in specimens from third molar extractions or gnathic bone resections containing unerupted teeth. The clinicoradiologic information provided by the submitting surgeon, as well as the clinical assessment
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Fig. 5 – Tooth follicle is composed of collagenous connective tissue with scattered myxoid change and epithelial remnants. The epithelium may be surround by a hyaline like change in the immediate adjacent connective tissue.The dental papilla is composed of myxoid stroma and may be lined by remnants of odontoblasts. (H&E; original magnification, 100 ). of unerupted teeth with an associated “cyst,” should aid in the distinction.
Pseudoneoplasms of salivary gland tissue Necrotizing sialometaplasia A number of different lesions can present as a pseudoneoplasm of salivary gland tissues. However, the one lesion with the greatest possibility of being misdiagnosed as a malignant neoplasm is necrotizing sialometaplasia (NSM).14,15 This uncommon condition affects primarily minor salivary gland tissues or seromucous glands located throughout mucosal surfaces of the head and neck. NSM can occur in any site
containing minor seromucous glands such as the larynx and sinonasal tract but is most frequently seen in the palate.16,17 The key histologic features of the process are lobular mucus acinar necrosis and accompanying proliferative squamous metaplasia of the remaining lobular duct system of the seromucous unit affected. Clinically, the resulting finding is a crater-like depression, with or without associated ulceration, and markedly delayed healing of the clinical lesion. The lesion is usually asymptomatic and may or may not be associated with an inciting traumatic event. Microscopic examination shows partial necrosis of mucinous acini within their lobular arrangement (Fig. 6). Squamous metaplasia of the ducts may show reactivate atypia; however, the proliferation remains within the confines of the minor gland tissue perimeter. Depending on the orientation and depth of the
Fig. 6 – The loss of seromucous acini is striking in both examples of NSM, respiratory mucosa and palate. The squamous metaplasia is prominent in the remaining ducts and retains a lobular arrangement. These key features are easy to assess in an adequate biopsy of the process (H&E; original magnification, 100 ).
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Fig. 7 – The late phase of EAF shows extensive fibrosis. A low-power review shows loss of the normal architectural structure in this nasal mucosa biopsy. The whorled “onion skinning” fibrosis and arterioles with scattered stromal inflammatory cells and eosinophils is readily identifed at higher power examination (H&E; original magnifications, 40 and 200 ).
incisional biopsy, the histologic assessment may be adequate. Lack of atypical mitotic features and the retention of lobular architecture are the key features to a correct diagnosis.
Pseudoneoplasms of sinonasal tract and larynx
positive plasma cell infiltrate. There is no overt evidence of obliterative vasculitis in EAF, a finding that is prominent in other IgG4-related diseases.19 The predominance of the eosinophil infiltrate is noted throughout all phases of the disease. The prognosis of sinonasal EAF is indolent progressive clinical course. The primary mode of management is surgical; however, there are reported responses to immunotherapy.19
Eosinophilic angiocentric fibrosis
Sinonasal hamartomas Eosinophilic angiocentric fibrosis (EAF) is an enigmatic disease that can affect the nasal cavity, lacrimal glands, nasal sinuses, larynx, and lower respiratory track. Sinonasal EAF is an uncommon tumefactive lesion which mimics a neoplastic disorder. This condition is currently considered to be in the spectrum of the IgG4-related systemic diseases.18,19 The histology of the late phase of EAS is composed of small caliber arterioles surrounded by concentric layers of fibrosis “onion skinning.” The inflammatory cells are lymphoplasmacytic with a prominent eosinophil cell component. The histology of the early phase of EAF differs from the later phase. The inflammatory cells predominate in the early phase with progressive increase in the whorling fibrosis around arterioles (Fig. 7). Staining for IgG4 for plasma cells will demonstrate their presence within a background of IgG
Respiratory epithelial adenomatoid hamartoma The vast majority of sinonasal tract hamartomas are pure epithelial types, although pure mesenchymal types exist as well as mixed types. On clinical or radiological examination, these lesions may present is a polypoid mass usually without aggressive destruction of bone. Among the pure epithelial type hamartomas that may be encountered in sinonasal biopsy specimens is respiratory epithelial adenomatoid hamartoma (REAH). This lesion is most often noted in specimens from male patients with a polypoid mass located in the posterior nasal cavity or inferior turbinate, ethmoid, and maxillary sinuses. Since the original description of REAH in 1995, other associated features such as seromucus
Fig. 8 – This polypoid fragment of REAH illustrates the continium of the surface lining with the subepithelial hamartomatous lesion. The ductal structures are lined by a goblet cell-like mucous epithelium with cilia and are surrounded by a thickened basement membrane (H&E; original magnifications, 40 and 200 ).
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Fig. 9 – Lobulated growth of chondroid matrix within a mesenchymal like spindled stroma characterizes the NCMH (H&E; original magnification, 200 ).
hamartoma have been described. Histologically, REAH is composed of dilated small to medium caliber glands lined by ciliated respiratory epithelium, which often have a continuation with the surface epithelium. The glands are surrounded by a thickened eosinophilic basement membrane (Fig. 8). The possibility of progression and/or association of REAH, and glandular hamartomas with low-grade sinonasal adenocarcinomas is yet to be completely characterized.20-22 REAH lesion is currently best classified as inflammatoryrelated lesion.23
Mesenchymal hamartoma Nasal masses in children and young adults are infrequently encountered. Most nasal masses represent developmental anomalies such as encephalocele, nasal gliomas, nasolacrimal duct cyst and some hamartomatous lesions.24,25 There is a rare and benign lesion known as nasal chondromesenchymal hamartoma (NCMH) that occurs within the cranial facial bones, usually sinonasal region. The lesion may also be present as a congenital mass. The common clinical differential diagnosis for this lesion includes sarcoma or meningoencephalocele. The characteristic histologic features are a mixed stromal with chondroid tissue with a lobulated growth pattern (Fig. 9). The lesion is reminiscent of mesenchymal hamartoma of the chest wall. Interestingly, there has been a recent reporting of this lesion being associated with germline and somatic mutations of DICER 1.26 Management for this lesion is complete excision of the mass. At this point there is no known malignant transformation within these lesions and rarely do they recur when completely excised.
re fe r en ces
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24. Ozolek JA, Carrau R, Barnes L, Hunt JL. Nasal chondromesenchymal hamartoma in older children and adults. Arch Pathol Lab Med. 2005;129:1444–1450. 25. Chandra M, Sharma N, Venkatachalam VP. Nasal chondromesenchymal hamartoma: a case report and review of literature. JK-Practitioner. 2014;19(1-2):53–59.
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26. Stewart DR, Messinger Y, Williams GM, et al. Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor-predisposition disorder. Hum Genet. 2014;133 (1):1443–1450.