PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms Topic 16: Submucosa: Reactive Conditions and Neoplasms Introduction Neoplasms Neoplasms Arising from <a href="/keyword/salivary-glands/" >salivary glands</a> General Features Benign Mixed Tumor (Pleomorphic Adenoma) Adenoid Cystic Carcinoma Mucoepidermoid Carcinoma Neoplasms Arising from Nerves Neurilemoma Neurofibroma Granular Cell Tumor Congenital Epulis of the Newborn Neoplasms Arising from Soft Tissues Lipoma Fibrosarcoma References Learning Guide Objectives Definitions Workbook Web Site Images Study Questions Terms and Definitions &quot;Flash Cards&quot; Disease Features &quot;Flash Cards&quot; Web Reader with Images Reader/Learning Guides PDF Reactive Conditions Mucous Retention Cyst Traumatic Neuroma Sialolithiasis Necrotizing Sialometaplasia 2009 William H. Crawford, Jr., D.D.S., M.S. All rights reserved. Copying for commercial purposes is prohibited. 265 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms Submucosal &quot;Bumps&quot; There are a number of diseases arising from tissues under the oral surface epithelium causing &quot;bumps&quot; covered with normal oral mucosa. They may arise from neoplastic transformations or from reactive changes to minor <a href="/keyword/salivary-glands/" >salivary glands</a> and nerves native to the submucosa. Neoplasms Salivary Gland Tumors General Features of Salivary Gland Neoplasms It will be remembered that much emphasis was placed on the recognition of the early stages of oral squamous cell carcinoma; any flat red, white, or red/white lesion should be considered to be oral SCC until proven otherwise. Now it is time to emphasize another potential dangerous group of neoplasms--the salivary gland tumors. These lesions may arise in the major <a href="/keyword/salivary-glands/" >salivary glands</a> (parotid, submandibular, sublingual); they may arise within minor <a href="/keyword/salivary-glands/" >salivary glands</a> as well. It is the location of the minor glands that requires the same attention of the clinician. Etiology and Pathogenesis The cause of minor salivary gland tumors is unknown. It is presumed that most common salivary gland neoplasms arise from ductal, not secretory epithelium. Clinical Features Minor salivary gland neoplasms appear as submucosal masses causing an elevation of the mucosal surface as they increase in size. In slow-growing benign neoplasms, the overlying mucosa is usually unaffected appearing the same color and texture as surrounding mucosa. However, faster-growing malignant neoplasms may cause ulceration of the mucosal surface; as a consequence of this feature, any ulcerated submucosal mass should be viewed with alarm. Other alarming features of salivary gland tumors include paresthesia (sensory nerves, V) and paralysis (motor nerves, VII). While some arise in youngsters, most of these as well as most arise in middle-aged or older adults. Pleomorphic Adenoma (Benign Mixed Tumor( Microscopic Features Mixed tumors are composed of neoplastic parenchyma (epithelium) and stroma (connective tissue). The epithelial component consists of countless duct-like structures that may be empty or filled with salivary secretions. It is the varied appearance of the stroma, however, that is most helpful in making the diagnosis of mixed tumor. The stroma may be a mixture of dense fibrous c.t., loose mesenchymal c.t., and cartilage. The neoplasm is invariably well-demarcated by a fibrous c.t. capsule. However, sometimes the capsule is incomplete or shows the presence of neoplastic cells. Prognosis and Treatment Mixed tumors must be surgically excised. Because the neoplasm is encapsulated, simple enucleation should suffice. In cases of parotid mixed tumors, however, the nearness of the facial nerve (cranial nerve VII) may cause the surgeon to be tentative about complete removal. In these cases and in the cases of capsule permeation, recurrences may occur. Malignant &quot;Transformation&quot; A malignant version of benign mixed tumor exists. This version is thought to arise from an untreated benign mixed tumor. While such transformation is a remote possibility, it serves as a reminder that all submucosal nodules in and around the oral cavity must be removed and submitted for microscopic examination. Adenoid Cystic Carcinoma Microscopic Features There are two microscopic features that distinguish this malignancy from other salivary gland neoplasms. First, it is composed largely of malignant epithelial cells arranged in sheets of dilated duct cross-sections 266 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms resembling a honeycomb or Swiss cheese. Second, it is common to find malignant epithelial cells invading the sheaths of nearby nerves (perineural invasion) a feature not commonly seen in other malignancies. In addition to bone invasion, adenoid cystic carcinoma often metastasizes to the lungs. Oddly, it does not spread to regional lymph nodes. Prognosis and Treatment As primary radiation is ineffective for these lesions, surgical excision is the treatment of choice for eradication of adenoid cystic carcinoma. The long-term prognosis of this disease, however, is not good. Mucoepidermoid Carcinoma General Features As its name indicates, mucoepidermoid carcinomas are composed of mucous secretory and ductal (stratified squamous) epithelia. The proportions of these tissues have been equated to long-term patient survival and have lead to the identification of &quot;low grade&quot; and &quot;high grade&quot; mucoepidermoid carcinomas. In the low grade varieties, mucous-secreting epithelial cells predominate while in the high grade version squamous ductal epithelium is the common tissue. Prognosis and Treatment Mucoepidermoid carcinomas are treated by surgical excision. The cure rates of the low grade variety approach 90% while cure rates of high grade mucoepidermoid carcinomas are about 50%. Neoplasms Arising from Nerves General Features If one thinks about it for even a moment, it is obvious that peripheral nerves abound in oral cavity connective tissue and bone. It is not surprising, then, that neoplasms may arise from these nerves from time to time. The etiology and pathogenesis of peripheral nerve tumors is unknown. However, a form of one lesion, the neurofibroma, is surely inherited as an autosomal dominant trait. Such a genetic etiology has not been identified with other nerve tumors. Since peripheral nerves are found both in the oral connective tissues and in bone, nerve neoplasms may also arise in either site. When arising under the mucosa, these lesions manifest as a submucosal nodule raising the surface epithelium. These submucosal lesions are usually solitary however, one lesion, again the neurofibroma, may be multiple. All the neoplasms to be summarized below are benign lesions; however, the neurofibroma may, in time, become malignant. Neurilemoma (Schwannoma) Origins The neurilemoma arises from the sheath of peripheral nerves. It usually occurs as an encapsulated single lesion that has a distinctive microscopic appearance. Microscopic Features It is composed of two types of tissue designated as &quot;Antoni A&quot; and &quot;Antoni B.&quot; The &quot;A&quot; tissue is composed of very regular patterns of nuclei and intervening tissue forming structures known as &quot;Verocay bodies&quot; while the &quot;B&quot; tissue is less regularly arranged. Prognosis and Treatment Adequate surgical excision of neurilemomas is curative. Recurrences or malignant transformation do not occur. Neurofibroma General Features The solitary neurofibroma can be readily eliminated while the multiple form (Von Recklinghausen's or Elephant Man's disease) the inherited progressive form of the disease, is incurable. 267 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms Microscopic Features Neurofibromas, whether solitary or multiple are composed of a jumble of proliferating elongated nerve sheath cells. They are not encapsulated nor do they contain Antoni A or B tissue. As already mentioned, a solitary neurofibroma is readily cured by adequate excision. Von Recklinghausen's Disease (Multiple Neurofibromatosus) Von Recklinghausen's form of the disease (multiple neurofibromas) is the serious form of the disease. In this condition, a patient will develop hundreds of neurofibromas with disfiguring results. It is also likely that one or more of these lesions will undergo malignant degeneration forming neurofibrosarcomas--an event that may cause death. Granular Cell Tumor (Granular Cell Myoblastoma) Clinical Features and Origin Unlike the other nerve lesions presented above, the granular cell tumor occurs most commonly in the tongue. It is usually found on the tongue's dorsal or lateral surfaces. While once thought to arise from skeletal muscle, it is now known to be derived from peripheral nerve sheaths. Microscopic Features As its name suggests, the granular cell tumor is composed mostly of large pale-staining cells filled with fine granules. The only complication associated with the microscopic features of this lesion is the presence of pseudoepitheliomatous hyperplasia in the overlying epithelium. This hyperplasia is so prominent that pathologists have mistaken this innocuous lesion with the much more serious oral squamous cell carcinoma. Prognosis and Treatment Adequate excision of granular cell tumors results in cure without recurrences. Removal of adequate tissue for biopsy will invariably reveal the granular cells that indicate the true benign nature of the neoplasm in spite of distracting pseudoepitheliomatous hyperplasia. Remembering that oral squamous cell carcinoma rarely affects the tongue dorsum and that granular cell tumors are submucosal lesions should prevent disastrous over treatment of this harmless lesion. Granular Cell Tumor of the Newborn (Congenital Epulis) General Features The congenital epulis is a benign oral growth occurring occasionally in newborn infants. They are usually single but rarely may be multiple. The fact that this condition is known by several names suggests that controversy surrounds it. Some authors are reverting to the name use here; the term indicates that (1) it appears at birth (congenital), (2) it occurs on the &quot;gums&quot; (epulis). Clinical Features It appears as a smooth polypoid exophytic growth arising (usually) from the alveolar ridge where teeth will some day erupt. Microscopic Features Microscopically it is composed of granular cells reminiscent of the granular cell tumor seen in adults. This finding led to use of the term &quot;congenital granular cell tumor.&quot; However, there are two findings that dispelled the congenital epulis as being a variant of the adult granular cell tumor. First, there is no pseudoepitheliomatous hyperplasia in the congenital epulis. Second, EM and histochemical findings reveal that the two are distinct entities. Prognosis and Treatment The congenital epulis is treated by local surgical excision. Recurrences do not occur. There are reported cases of the lesion resolving in time with out treatment. Soft Tissue Tumors Lipoma General Features The cause of lipomas is unknown. These lesions arise wherever there is adipose connective tissue in the oral submucosa. As the neoplasm enlarges and approaches the surface, it may appear a light yellow color. The 268 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms mucosa covering the lesion is usually the same color and texture as the surrounding mucosa. Lipomas are composed of well-differentiated fat cells that are indistinguishable from normal adipose connective tissue. Surgical excision of lipomas is curative. Rare recurrences are related to their incomplete removal. Fibrosarcoma General Features Fibrosarcomas are malignant neoplasms of fibroblasts. They are not common neoplasms anywhere; about 10% occur in the head and neck. Some fibrosarcomas are slow growing well-differentiated malignancies while others are rapidly growing poorly differentiated lesions. Fibrosarcomas virtually can arise anywhere. They are usually treated by surgical removal. Even well differentiated fibrosarcomas may be difficult to remove completely; they may recur. About 50% survive five years after surgery. Reactive Conditions Mucous Retention Cyst General Features Occasionally microscopic examination of a lesion clinically resembling a mucous escape phenomenon reveals an epithelial lining separating accumulated saliva from the surrounding connective tissue. When such an epithelial lining is identified, the diagnosis of &quot;mucous retention cyst&quot; is made. This cyst is presumed to arise by retention of saliva within a salivary gland excretory duct. Continued accumulation of saliva causes the duct to become distended producing a clinical swelling resembling a mucous escape phenomenon. The epithelium surrounding the saliva identified on microscopic examination is, of course, the lining of the dilated duct. Mucous retention cysts are treated by simple excision; recurrence is very uncommon. Traumatic Neuroma (Amputation Neuroma) Etiology and Pathogenesis The traumatic neuroma is probably not a neoplasm at all but merely a reaction of peripheral nerves to local injury. It apparently arises in the aftermath of cutting a peripheral nerve during surgical or traumatic episodes. During subsequent regeneration, the peripheral nerve axons cannot find their way into the severed nerve sheath but rather form a painful disorganized mass in the area of injury. Microscopic Features Traumatic neuromas are recognized microscopically by the presence of a jumble of small peripheral nerve fiber--a feature that readily distinguishes it from the neurilemoma and neurofibroma. Simple surgical excision cures these lesions; they rarely recur and never transform into more dangerous lesions. Sialolithiasis Etiology and Pathogenesis Translated, &quot;sialolithiasis&quot; means a condition of (-iasis) salivary (sialo-) stones (-lith-). The stones referenced in the name are made of calcium forming around debris within salivary gland ducts. The mentioned debris is assumed to be composed of mucus mixed with cells shed from the duct lining; this is supposed to constitute a &quot;nidus&quot; around which calcium salts are deposited. After being deposited concentrically, a stone is constructed. Clinical and Radiographic Features Salivary stones most commonly appear in Wharton's duct draining the submandibular gland. Often, there is pain especially at mealtime. If the stone is near the surface, it may be seen and palpated. More often, however, they are located away from the surface; radiography is necessary to identify these deep stones. Mandibular occlusal radiographs are usually successful in visualizing the stone as a radiopaque structure. Submandibular stones may appear on panoramic or periapical films superimposing a radiopaque &quot;shadow&quot; on other structures. In such cases, a mandibular occlusal film will settle the issue. 269 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms Prognosis and Treatment Superficially located stones may be &quot;milked&quot; from the duct by palpation; surgery is often required for deeper stones. Necrotizing Sialometaplasia sEtiology and Pathogenesis Necrotizing sialometaplasia is harmless uncommon condition of the hard palate mimicking more serious diseases. It is presumed to be caused by ischemia to the minor <a href="/keyword/salivary-glands/" >salivary glands</a> located in the hard palate. This ischemia causes infarction of salivary gland acini followed by an inflammatory reaction. Clinical Features Early changes produce a palatal swelling followed later by an ominous-appearing ulcer. Since these changes may suggest more serious diseases such as salivary gland neoplasms, fungal infestations, or squamous cell carcinomas biopsy is often necessary to rule them out. Microscopic Features Microscopic examination will reveal coagulation necrosis of salivary gland acini and surrounding inflammation without neoplastic or infectious features. Once correctly diagnosed, no treatment is required for necrotizing sialometaplasia, as the condition will resolve by itself. References: Kumar, Abbas, Fausto: Robbins and Cotran Pathologic Basis of Disease. Elsevier-Saunders, Seventh Edition, 2005. Neville, Damm, Allen, Bouquot: Oral &amp; Maxillofacial Pathology. Saunders, Second Edition, 2002. Sapp, Eversole, Wysocki: Contemporary Oral and Maxillofacial Pathology. Mosby, Second Edition, 2004. Learning Guide 1. After completion of this chapter the student should be able to write and identify the definitions of the following items in 3 below. write and identify whether pyogenic granuloma, irritation fibroma, pregnancy tumor, and epulis granulomatosum are a) red, b) possess granulation tissue, c) are caused by trauma, and d) are related to increased hormone levels. write and identify whether epulis fissuratum, inflammatory papillary hyperplasia, mucocele, and ranula are a) related to dentures, b) occur on the hard palate, c) occur on the floor of the mouth, d) are fluid filled. 2. Associate (by identifying them) the following prefixes/suffixes and their meanings. In other words, when confronted with these prefixes/suffixess, be able to pick the correct term/definition from a list (multiple choice or matching). con iasis lipo with, together pathologic condition of fat muco sialo mucus, mucosa <a href="/keyword/salivary-glands/" >salivary glands</a> , saliva 270 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms 3. Associate (by identifying them) the following terms and their definitions. In other words, when confronted with the term or definition of the following, be able to pick the correct term/definition from a list (multiple choice or matching). Adenoid Cystic Carcinoma Congenital Epulis Granular Cell Tumor Lipoma Mucoepidermoid Carcinoma Mucous Retention Cyst Necrotizing Sialometaplasia Neurilemoma Neurofibroma Neurofibromatosis Perineural Invasion Pleomorphic Adenoma A dangerous malignancy arising in major or minor <a href="/keyword/salivary-glands/" >salivary glands</a> that tends to invade and spread along nerves. A benign polypoid exophytic lesion that may appear on the toothbearing gingiva of a newborn. A benign tumor arising from nerve sheaths that usually occurs in the tongue; not associated with more serious disease. A benign neoplasm of fat that may arise in the oral submucosal tissues. A malignant neoplasm of major or minor <a href="/keyword/salivary-glands/" >salivary glands</a> ; some are very malignant, others are almost benign. A true cyst resembling a mucous escape phenomenon but lined with duct epithelium An infarct of minor salivary gland acini in the hard palate; may produce a palatal ulcer mimicking SCC. A benign neoplasm of nerve sheaths; usually solitary has no relation to other more serious disease. A benign neoplasm of nerve sheaths; may be multiple and progressive. Yet another name for Von Recklinghausen's disease. Invasion of nerve sheaths by malignant cells; a characteristic of adenoid cystic carcinoma. A benign neoplasm of <a href="/keyword/salivary-glands/" >salivary glands</a> in which the parenchyma (glandular epithelium) and stroma (connective tissue) is neoplastic; some call it &quot;benign mixed tumor.&quot; A salivary duct stone; most common in Wharton's duct of the submandibular gland. A lesion arising in the connective tissues under mucous membranes. Tumor-like overgrowth of peripheral nerves resulting from trauma. Multiple hereditary neurofibromas; may cause serious disfigurement and malignant transformation. Sialolithiasis Submucosal Mass Traumatic Neuroma Von Recklinghausen's Disease 271 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms 4. Match the following conditions with the appropriate printed characteristics: Mucoepidermoid Carcinoma Characteristic Unexplained paresthesia common May be intraoral Malignant Epithelium and c.t. are neoplastic &quot;High&quot; and &quot;low grades&quot; may occur May manifest as an intraoral &quot;bump&quot; Cartilage, loose and dense c.t. may occur &quot;Honeycombed&quot; microscopic appearance Tumor cells often seen around nerves 272 Adenoid Cystic Carcinoma Pleomorphic Adenoma PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms 5. Match the following conditions with the appropriate printed characteristics: Granular Cell Tumor Traumatic Neuroma Characteristic Lipoma May be multiple Yellow appearance May appear as a submucosal nodule Usually solitary Cafe-au-lait spots Microscopic features may resemble SCC Appears in newborn infants Development may follow oral surgery Usually appears in the tongue Multiple form is an inherited trait Also known by the term &quot;myoblastoma&quot; Responsible for Von Recklinghausen's disease Has &quot;A&quot; and &quot;B&quot; tissue Congenital Epulis Neurofibroma Neurilemoma 273 PTHL 312b: Oral and Maxillofacial Pathology Submucosa: Reactive Conditions &amp; Neoplasms 6. Match the following conditions with the appropriate printed features:. Adenoid Cystic Carcinoma Pleomorphic Adenoma Granular Cell Tumor Epithelial neoplasm May appear on the lateral hard palate May cause wide-spread deformities May cause a submucosal swelling A synonym contains &quot;amputation&quot; May contain pseudoepitheliomatous hyperplasia Composed of &quot;jumbled nerves&quot; Usually encapsulated May metastasize widely 7. After reading the following fictitious histories, place the appropriate following words or phrases in empty cell opposite the appropriate history:. Adenoid Cystic Carcinoma Pleomorphic Adenoma Submucosal Swelling History Examination of a 35 year-old female revealed a firm swelling in her right hard palate. Biopsy revealed that the lesion was composed of &quot;ductal epithelium that showed no signs of anaplasia or invasion. Examination of a 42 year-old male revealed a firm swelling in his upper lip. Biopsy revealed that the lesion was composed of dark cells arranged in a &quot;honey combed&quot; fashion; there was also evidence of nerve invasion. 274 Neurofibroma Feature Traumatic Neuroma Lipoma