Salivary Gland Pathology

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1 IN THE NAME OF GOD

2 Salivary Gland Pathology CHAPTER 11 Dr.kheirandish Oral and maxillofacial pathology

3 Sialadenosis Adenomatoid Hyperplasia of the Minor Salivary Glands Necrotizing Sialometaplasia Pleomorphic Adenoma Oncocytoma

4 Sialadenosis (Sialosis) Unusual Noninflammatory disorder Salivary gland enlargement Parotid glands Underlying systemic problem Endocrine, nutritional, or neurogenic Diabetes mellitus, general malnutrition, alcoholism, and bulimia

5 Dysregulation of the autonomic innervation of the salivary acini Accumulation of secretory granules : enlargement of the acinar cells. CLINICAL FEATURES Slowly evolving swelling May or may not be painful Usually bilateral Submandibular glands Minor salivary glands : rare

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7 HISTOPATHOLOGIC FEATURES Hypertrophy of the acinar cells Two to three times greater than normal size. Nuclei are displaced to the cell base Cytoplasm is engorged with zymogen granules Treatment Control of the underlying cause. Cosmetic concern : partial parotidectomy

8 ADENOMATOID HYPERPLASIA OF THE MINOR SALIVARY GLANDS Rare lesion Minor salivary glands Mimics a neoplasm Pseudotumor Hard or soft palate Local trauma

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10 HISTOPATHOLOGIC FEATURES Normal-appearing mucous acini Greater in number than normally Increased in size Chronic inflammation TREATMENT Biopsy is necessary

11 NECROTIZING SIALOMETAPLASIA Uncommon Locally destructive Inflammatory condition Ischemia leads to local infarction Mimics a malignant process, both clinically and microscopically.

12 Predisposing factors : Traumatic injuries Dental injections Ill-fitting dentures Upper respiratory infections Adjacent tumors Previous surgery Compromising the blood supply to the involved glands, resulting in ischemic necrosis. However, many cases occur without any known predisposing factors.

13 CLINICAL FEATURES Palatal salivary glands More than 75% : posterior palate Hard palate Two thirds : unilateral Any age Adults

14 CLINICAL FEATURES Males : twice time Initially : nonulcerated swelling, often associated with pain or paresthesia Within 2 to 3 weeks, necrotic tissue sloughs out, leaving a craterlike ulcer ( 1 cm to more than 5 cm in diameter) A part of my palate fell out." At this point, the pain often subsides

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16 HISTOPATHOLOGIC FEATURES Acinar necrosis in early lesions, followed by associated squamous metaplasia (ducts) lobular architecture : helpful histopathologic Squamous cell carcinoma(scc) or mucoepidermoid carcinoma(mec) Pseudoepitheliomatous hyperplasia Squamous proliferation has a bland cytologic appearance

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18 TREATMENT Biopsy usually is indicated to rule out the possibility of malignant disease. The lesion typically resolves on its own accord, with an average healing time of 5 to 6 weeks.

19 SALIVARY GLAND TUMORS Parotid gland most common site Pleomorphic adenom Mucoepidermoid carcinoma Submandibular gland Malignancy is double of the parotid gland Pleomorphic adenoma Adenoid cystic carcinoma Sublingual gland Rare 70% to 90% are malignant

20 SALIVARY GLAND TUMORS Minor salivary glands Palate : most frequent site Pleomorphic adenoma Mucoepidermoid carcinoma and adenoid cystic carcinoma Lips : second most common Upper lip Up to 91% of retromolar tumors and most tumors in the floor of the mouth and tongue are malignant.

21 PLEOMORPHIC ADENOMA (BENIGN MIXED TUMOR) Most common salivary neoplasm. The terms pleomorphic adenoma and mixed tumor both represent attempts to describe this tumor's unusual Histopathologic. Pleomorphic Mixed neoplasm : derived from more than one germ layer.

22 CLINICAL FEATURES Painless Slowly growing Firm mass Many months or years Any age (most common in young and middle-aged adults) Most common childhood Female Superficial lobe / 10% deep lobe

23 CLINICAL FEATURES Facial nerve palsy and pain are rare. Initially : movable / Grows larger: less mobile Bilateral (Parotid glands) : synchronous or metachronous Palate: posterior lateral aspect /smooth-surfaced/domeshaped masses/ not movable Upper lip : mobile Traumatized : secondary ulceration

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26 HISTOPATHOLOGIC FEATURES Well circumscribed, encapsulated tumor (may be incomplete or show infiltration by tumor cells). Encapsulation : minor gland tumors(palatal) Mixture of glandular epithelium and myoepithelial cells within a mesenchyme-like background. Variable ratio of the epithelial elements and the mesenchyme-like component

27 Epithelium : ducts and cystic structures / islands or sheets Myoepithelial cells : large percentage /variable morphology (angular or spindle) Plasmacytoid myoepithelial cells (minor glands) Stromal" changes (myoepithelial cells) Mucoid Myxomatous Chondroid Hyalinized Osteoid Fat Myoepithelioma : No ductal elements.

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30 TREATMENT Surgical excision Superficial lobe : superficial parotidectomy ( preservation of the facial nerve) Deep lobe : total parotidectomy (preservation of the facial nerve) Local enucleation:should be avoided Submandibular tumors : total removal Adequate surgery: excellent prognosis Predominantly myxoid : more recurrence Carcinoma ex pleomorphic adenoma

31 ONCOCYTE o Large epithelial cells o Greek word onkoustai (swell) o Swollen granular cytoplasm o Mitochondria o Focal oncocytic metaplasia :age o Uncommon :younger than 50 o Other organs: thyroid, parathyroid, and kidney.

32 ONCOCYTOMA (OXYPHILIC ADENOMA) Older adults(eighth decade) Female Major salivary glands(parotid) Firm Slowly growing Painless Superficial lobe Bilateral Benign Oncocytes Rare

33 HISTOPATHOLOGIC FEATURES Well circumscribed Sheets of large polyhedral cells (oncocytes) Abundant granular. Eosinophilic cytoplasm Centrally nuclei (small and hyperchromatic to large and vesicular). Little stroma Mitochondria(electron microscopy) light microscopic Phosphotungstic acid hematoxylin (PTAH) Glycogen : periodic acid-schiff (PAS) Clear cells

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35 TREATMENT Surgical excision Partial parotidectomy Submandibular gland (total removal) Low rate of recurrence Malignant oncocytomas

36 IN THE NAME OF GOD

37 ONCOCYTOSIS (NODULAR ONCOCYTIC HYPERPLASIA) Oncocytic metaplasia Transformation of ductal and acinar cells to oncocytes Older than 50 y/o Both the proliferation and the accumulation of oncocytes Mimic a tumor (clinically and microscopically)

38 CLINICAL FEATURES Parotid gland Proliferation is multifocal and nodular Entire gland can be replaced by oncocytes HISTOPATHOLOGIC FEATURES Focal nodular collections of oncocytes Oncocytoma

39 WARTHIN TUMOR (PAPILLARY CYSTADENOMA LYMPHOMATOSUM) Benign Parotid gland Second most common benign parotid Tumor Adenolymphoma : should be avoided Smoking Polyclonal : tumorlike

40 Pathogenesis : uncertain Hypothesis 1)Heterotopic salivary gland tissue found within parotid lymph nodes 2)Proliferation of salivary gland ductal epithelium that is associated with secondary formation of lymphoid tissue

41 Older adults (sixth and seventh decades) Whites Male (10: 1) Smoking and bilaterality.

42 Slowly growing Painless Nodular mass Firm or fluctuant Parotid tail Bilaterally (metachronous) Submandibular or minor salivary glands

43 HISTOPATHOLOGIC FEATURES Papillary cystadenoma Iymphomatosum Ductal epithelium and a lymphoid stroma Epithelium (oncocytic nature)

44 Two layers : A) inner luminal layer tall columnar cells with centrally placed, palisaded, and slightly hyperchromatic nuclei. B) second layer of cuboidal or polygonal multiple papillary cells with more vesicular nuclei Cystic spaces Multiple papillary infoldings lymphoid stroma

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46 TREATMENT AND PROGNOSIS Surgical removal Superficial parotidectomy Malignant Warthin tumors (carcinoma ex papillary cystadenoma Iymphomatosum)

47 MONOMORPHIC ADENOMA Benign salivary gland tumors demonstrating a more uniform histopathologic pattern than the common pleomorphic adenoma. Basal cell adenoma Canalicular adenoma

48 CANALICULAR ADENOMA Female Slowly growing Painless mass Firm or fluctuant Mucocele

49 Uncommon Minor salivary glands Upper lip Parotid gland Older adults

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51 HISTOPATHOLOGIC FEATURES Fibrous capsule Single-layered cords of columnar or cuboidal epithelial cells with deeply basophilic nuclei Ductal structures Cystic spaces Papillary projections

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53 BASAL CELL ADENOMA Benign Uncommon Basaloid appearance Parotid gland Minor glands : second most common site Middle-aged and older adults Women

54 Slowly growing Movable mass Superficial lobe Membranous basal cell adenoma Hereditary Combination with skin appendage tumors (dermal cylindromas and trichoepitheliomas) Multiple bilateral Dermal analogue tumors

55 HISTOPATHOLOGIC FEATURES Encapsulated or well circumscribed Ductal epithelium and myoepithelial cells Subtypes : 1. Solid (Most common subtype) 2. Trabecular 3. Tubular 4. Membranous

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57 Solid subtype : Multiple islands and cords of epithelial cells Fibrous stroma Peripheral cells (palisaded and cuboidal to columnar) Basal cell carcinoma Central cells

58 Tubular subtype: Is characterized by the formation of small, round, duct-like structures. Trabecular subtype: Demonstrates narrow cordlike epithelial strands

59 Membranous basal cell adenoma : Multiple Large lobular islands Jigsaw puzzle fashion Similar to dermal cylindroma,

60 TREATMENT AND PROGNOSIS Complete surgical removal Recurrence is rare, BUT membranous subtype has a 25% to 37% recurrence rate Malignant counterpart (basal cell adenocarcinoma)

61 DUCTAL PAPILLOMAS 1) SIALADENOMA PAPILLIFERUM 2) INTRADUCTAL PAPILLOMA 3) INVERTED DUCTAL PAPILLOMA

62 Microscopically : papillomatous pattern Rare Squamous papilloma

63 SIALADENOMA PAPILLIFERUM Minor salivary glands (palate) Older adults Male Exophytic Papillary surface Clinically similar to the squamous papilloma

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65 HISTOPATHOLOGIC FEATURES Similar to the squamous papilloma Exophytic papillary projections Covered by stratified squamous epithelium Cutaneous syringocystadenoma papilliferum

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67 INTRADUCTAL PAPILLOMA Ill-defined lesion Adults Minor salivary glands Submucosal swelling HISTOPATHOLOGIC FEATURES Unicystic structure Cuboidal or columnar epithelium Papillary projections into the cystic lumen

68 INVERTED DUCTAL PAPILLOMA Rare Minor salivary glands Adults Lower lip and mandibular vestibule Asymptomatic nodule HISTOPATHOLOGIC FEATURES Proliferation of squamoid epithelium Multiple thick, bulbous papillary projections that fill the ductal lumen

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71 TREATMENT AND PROGNOSIS Conservative surgical excision Recurrence is rare

72 MUCOEPIDERMOID CARCINOMA One of the most common salivary gland malignancies Second to seventh decades Most common malignant salivary gland tumor in children Previous history of radiation therapy to the head and neck Parotid gland Asymptomatic swelling

73 Pain or facial nerve palsy (high-grade tumors) Minor glands : second most common site (palate) Mucocele Intraosseous Lower lip. floor of mouth. tongue. and retromolar pad areas are uncommon locations for salivary gland neoplasia. the mucoepidermoid carcinoma is the most common salivary tumor in each of these sites.

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75 HISTOPATHOLOGIC FEATURES A. Mucus-producing cells : Abundant foamy cytoplasm Mucin stains + B. Squamous (epidermoid) cells : Squamoid features Polygonal Shape C. Intermediate cells : Progenitor of both the mucous and the epidermoid cells Vary in appearance ( small. Basaloid) Clear cells

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77 Traditionally categorized into three histopathologic grades : 1. Amount of cyst formation 2. Degree of cytologic atypia 3. Relative numbers of Mucous. Epidermoid and Intermediate cells

78 Low-grade tumors Prominent cyst formation Minimal cellular atypia High proportion of mucous cells High-grade tumors Solid islands of squamous and intermediate cells Pleomorphism Mitotic activity Mucus-producing cells (infrequent)

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80 Intermediate-grade tumors Between those of the low-grade and high-grade neoplasms Cyst formation occurs (less prominent than lowgrade) Cellular atypia +/_ All three major cell types are present, but intermediate cells usually predominate.

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82 TREATMENT AND PROGNOSIS Treatment : Location, Histopathologic grade, and Clinical stage Early-stage : parotidectomy (preservation of the facial nerve) Advanced : total removal of the parotid gland (sacrifice of the facial nerve) low-grade: modest margin of surrounding normal tissue removed High-grade or large : wider resection (involved bone must be excised)

83 Submandibular gland : total removal Radical neck dissection : Metastasis Large High-grade Postoperative radiation therapy (more aggressive tumors) Prognosis : depends on the grade and stage of the Submandibular gland tumors : poorer outlook than parotid gland

84 IN THE NAME OF GOD

85 INTRAOSSEOUS MUCOEPIDERMOID CARCINOMA (CENTRAL MUCOEPIDERMOID CARCINOMA) Rare Most common Adenoid cystic carcinoma, benign and malignant mixed tumors, adenocarcinoma, acinic cell adenocarcinoma, epithelial-myoepithelial carcinoma, and monomorphic adenoma.

86 Hypotheses : 1) Ectopic salivary 2) Sinus lining 3) Odontogenic epithelium (most likely source) o Association with impacted teeth or odontogenic cysts

87 Female (middle-aged adults) Mandible (molar-ramus area) Cortical swelling Pain, trismus, paresthesia Unilocular or multilocular radiolucency Well-defined borders Irregular and ill-defined area of bone destruction Unerupted tooth (odontogenic cyst or tumor)

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89 HISTOPATHOLOGIC FEATURES Similar to soft tissue counterpart Low-grade TREATMENT AND PROGNOSIS Radical surgical resection Adjunctive radiation therapy Metastasis Prognosis : good

90 ACINIC CELL ADENOCARCINOMA Serous acinar differentiation Acinic cell tumor Metastasis Death Low-grade malignancy

91 Parotid gland Submandibular gland, buccal mucosa, lips, palate Second to the seventh decades (40s) women Slowly growing Many months or years Asymptomatic Facial nerve paralysis : ominous sign for parotid tumors

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93 HISTOPATHOLOGIC FEATURES Highly variable Well circumscribed Most characteristic cell : serous acinar cell Abundant granular basophilic cytoplasm and a round. darkly Stained eccentric nucleus Uniform Mitotic activity : uncommon Clear cells

94 Growth patterns : 1. Solid : resembles normal parotid gland tissue 2. Micro cystic : small cystic spaces 3. Papillary-cystic : papillary projections into the cystic spaces 4. Follicular : similar to thyroid tissue

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96 TREATMENT AND PROGNOSIS Superficial lobectomy Total parotidectomy One of the better prognoses of any of the malignant salivary gland tumors The prognosis for minor gland tumors is better

97 MALIGNANT MIXED TUMORS : I. CARCINOMA EX PLEOMORPHIC ADENOMA (CARCINOMA EX MIXED TUMOR) I. CARCINOSARCOMA II. METASTASIZING MIXED TUMOR

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99 CARCINOMA EX PLEOMORPHIC ADENOMA Most common Malignant transformation of the epithelial component 15 years older than benign pleomorphic adenoma Sixth to eighth decades Mass (many years) Recent rapid growth

100 Pain Painless Ulceration Some tumors :short duration Risk for malignant change : duration Major glands : parotid gland Palate Facial nerve palsy

101 Variable microscopic appearance Areas of typical benign (most or only a small portion) Cellular pleomorphism Abnormal mitotic activity Poorly differentiated adenocarcinoma o Polymorphous lowgrade adenocarcinoma. salivary duct carcinoma. mucoepidermoid carcinoma, and adenoid cystic carcinoma.

102 Aggressive growth pattern Capsular invasion Noninvasive or carcinoma in situ ex mixed tumor

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104 Wide excision Local lymph node dissection Adjunctive radiation therapy Prognosis : guarded Histopathologic subtype of the malignant component In situ (noninvasive) carcinoma ex mixed tumor

105 CARCINOSARCOMA Rare Parotid gland Submandibular gland and minor salivary glands Clinical signs and symptoms(similar to those of the carcinoma ex pleomorphic Adenoma) Previous history of a benign pleomorphic adenoma De novo

106 Biphasic tumor Both carcinomatous and sarcomatous areas Epithelial component : poorly differentiated adenocarcinoma or an undifferentiated Carcinoma Sarcomatous portion : Chondrosarcoma (osteosarcoma. fibrosarcoma. liposarcoma. rhabdomyosarcoma. malignant fibrous histiocytoma) Evidence of an origin (benign mixed tumor)

107 Radical surgical excision Radiation therapy Chemotherapy Prognosis : poor Recurrent local tumor Metastases

108 METASTASIZING MIXED TUMOR Rare Parotid gland Submandibular gland or minor salivary glands Metastases (bones or lung) History of a benign mixed tumor Multiple recurrences

109 Benign microscopic appearance Both the primary and the metastatic sites Malignant histopathologic changes Surgical excision of both the primary tumor and the metastatic sites

110 ADENOID CYSTIC CARCINOMA ADCC Common Cylindroma Any salivary gland Minor salivary glands (palate) Parotid and submandibular glands

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112 Middle-aged adults Slowly growing Pain : common / important finding / early (before swelling) Facial nerve paralysis

113 HISTOPATHOLOGIC FEATURES Myoepithelial and ductal cells Varied arrangement Three major pattern : 1) Cribriform 2) Tubular 3) Solid Combination (predominant pattern)

114 Cribriform pattern: Most classic Islands Basaloid epithelial cells Multiple cylindrical, cystlike spaces (resembling Swiss cheese) Tumor cells : small / cuboidal / basophilic nuclei / little cytoplasm /uniform /mitotic activity is rarely Tubular pattern : Multiple small ducts or tubules

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116 Solid variant : Larger islands or sheets of tumor cells Cellular pleomorphism Mitotic activity Focal necrosis Perineural invasion (not pathognomonic)

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118 TREATMENT AND PROGNOSIS Local recurrence Distant metastasis Surgical excision Neck dissection - Prognosis : Poor

119 Late recurrence and metastasis (5-year survival rate has little significance) Solid pattern (worse outlook) Maxillary sinus and submandibular gland : poor prognosis Death : local recurrence or distant metastases Metastases : lungs and bones

120 POLYMORPHOUS LOW-GRADE ADENOCARCINOMA (LOBULAR CARCINOMA; TERMINAL DUCT CARCINOMA) Common Minor salivary Major glands : rare De novo Malignant component of a carcinoma ex pleomorphic adenoma

121 Palate Upper lip and buccal mucosa Females (Older adults) Painless mass Slow growth Erode or infiltrate the underlying bone

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123 HISTOPATHOLOGIC FEATURES Tumor cells : Uniform Round to polygonal Indistinct cell borders Nuclei : round, ovoid (pale staining) Different growth patterns : (polymorphous term) Solid / cords / ducts / cystic spaces / cribriform

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125 Mitotic : uncommon Well circumscribed Peripheral : infiltrative / single-file Perineural invasion : common Adenoid cystic carcinoma (different prognoses) Immunohistochemical staining : helpful

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127 TREATMENT AND PROGNOSIS Wide surgical excision (including underlying bone) Metastasis (regional lymph nodes): uncommon Distant metastasis : rare Overall prognosis : good

128 SALIVARY ADENOCARCINOMA, NOT OTHERWISE SPECIFIED (NOS) Diverse group of neoplasms Parotid gland Minor glands and submandibular gland

129 Asymptomatic Pain Facial nerve paralysis Microscopic : highly variable Low-grade neoplasms to high-grade malignancies

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