Oncocytic lesions of salivary gland

1. ONCOCYTIC LESIONS
OF SALIVARY GLAND
SHERIN JAMES
Dept. of Oral Pathology and Microbiology
1

2. CONTENTS
• Introduction
– History
– EM of oncocytes (mitochondria)
– Hypothesis for mitochondrial hyperplasia
– Oncocytic transformation
• Classification
• Each lesion wise
• Summary
• Conclusion
• References
2

3. INTRODUCTION
3

4. 4
Hamperl (1931) – oncocyte
Large granular cells in tissues of kidney, thyroid, parathyroid, pituitary and adrenal glands
Individual cells/cell aggregates : permanent modification as metaplastic process/
proliferation as hyperplastic or neoplastic process
Zimmermann
Oncocytes in sublingual gland
Pyknocytes : condensed nuclear chromatin/pyknotic nuclei
First described by Schaffer in 1897
Ductal and acinar elements of salivary glands (tongue, eosophagus and pharynx)
Result of degenerative phenomenon in salivary gland parenchymal cells
Blanck – not neoplasm, nodular hyperplasia
Adaptive/ compensatory hyperplastic cell – 2* somatic mutation

5. 5

6. 6
Light photomicrograph of parotid oncocyte - granular cytoplasm and round
centrally positioned nucleus (hematoxylin and eosin
stain, original magnification 120).

7. • Electron microscopic :
– Numerous mitochondria (hyperplasia) granules marked cytoplasmic
eosinophilia (light microscopy)
– Basis for hyperplasia of mitochondria : unknown
 Represent a form of cellular degeneration/regression (BO cell)
 Sign of ageing/ Functional exhaustion.
 Degenerative metaplasia
 Intracellular metabolic disturbance with mitochondropathy – age dependent
metblc defect
– Becker, Donath, Seifert
7

8. MITOCHONDRIA (EM OF
ONCOCYTES)
8
• Generate and expend large amounts of energy
• Increase in no. by division throughout interphase
• Possess their own genome, increase their nos. by
division and synthesize some of the structural
proteins

9. MITOCHONDRIAL DNA
• Closed circular molecule
• Of the 37 genes,
– 13 are for proteins (polypeptides),
– 22 are for transfer RNA (tRNA)
– 2 of ribosomal RNA (rRNA)
9
EM OF ONCOCYTES

10. ENZYMES AND ENZYME
SYSTEMS
OUTER MITOCHONDRIAL MEMBRANE
Mitochondrial porins
Receptors for proteins and
polypeptides
Several enzymes
(phospholipase A2,
monoamine oxidase,acetyl
CoA synthase.
10
EM OF ONCOCYTE
Mitochondria contain enzyme systems that generate ATP by means of citric acid
cycle and oxidative phosphorylation

11. HYPOTHESIS FOR HYPEPLASIA OF
MITOCHONDRIA
11
Alteration in
mitochondrial DNA
: change in number
of mitochondria
Organelle
containing own
genetic
information
DNA within
mitochondria
Compensatory
mechanism for
supplying enzymes
Exhaustion of
mitochondrial
enzymes/ enzyme
systems
Increasing age

12. ONCOCYTIC TRANSFORMATION
Early stages
• Non-oriented mitochondria increase
gradually in size and number in
cytoplasm of duct cells
Late stages
• Cytoplasm gets filled with tightly
packed randomly oriented
mitochondria, basal striations disappear
and nuclei show pyknotic appearance
12

13. ONCOCYTIC LESIONS
(benign/malignant tumours
exhibiting oncocytes)
13

14. CLASSIFICATION
• ONCOCYTIC LESIONS :
• Oncocytoma, Oncocytosis, Oncocytic carcinoma
• BENIGN LESIONS SHOWING ONCOCYTIC METAPLASIA :
• Pleomorphic Adenoma, Warthin’s tumour
• MALIGNANT LESIONS EXHIBITING ONCOCYTES:
• Mucoepidermoid carcinoma, Acinic cell carcinoma
14

15. Classification of oncocytic lesions
• World Health Organization : three distinct types
– Oncocytosis
– Oncocytoma
– Oncocytic carcinoma
16
Oghan F, Apuhan T, Guvey A. Rare Malignant Tumours of the Parotid Glands: Oncocytic Neoplasms. Neck
Dissection – Clinical Application and Recent Advances Feb 2012; 137-148.

16. Classification of oncocytic lesions
• Dardick :
17
Oncocytoma
Typical oncocytoma
Clear cell oncocytoma
Hybrid oncocytoma/
Warthin’s tumour
Oncoytic hyperplasia
Multifocal nodular oncocytic
hyperplasia
Diffuse oncocytosis
Oncocytic differentiation in
other salivary gland tumours
Borderline and malignant
oncocytic tumours
Aggresive/atypical
oncocytoma
Oncocytic adenocarcinoma

17. ONCOCYTIC LESIONS
(Oncocytoma , Oncocytosis , Oncocytic carcinoma)
18

18. TYPICAL ONCOCYTOMA
OXYPHILIC GRANULAR CELL ADENOMA
ACIDOPHILIC GRANULAR CELL TUMOR
ONCOCYTIC ADENOMA
ONCOCYTIC CELL ADENOMA
19

19. ONCOCYTOMA
• Discrete encapsulated tumour
• Characterized by presence of oncocytes
• No myoepithelial / basal cell participation
20

20. CLINICAL FEATURES
Site
Parotid gland -
Submandibular
palatal mucosa >
buccal mucosa > tongue Age
Older adults (mean age
:58-77 years)
No gender predilection
Cause
Radiation exposure to
the head and neck
region
21
ONCOCYTOMA

21. CLINICAL APPEARANCE
• Indistinguishable
• Indolent, single, often multilobulated, firm solid
mass in the superficial lobe of the parotid gland
• “Shelling out” with blunt dissection during
surgery
22
ONCOCYTOMA

22. CLINICAL APPEARANCE
• Deep lobe of the parotid gland
– Insinuated between branches of facial nerve
– Painless without facial nerve involvement
• Tumour size : varies with duration of lesion
• Generally does not exceed 4.0 cms
• Freely movable on palpation
• Intraoral oncocytomas
– No demonstration of definite clinical symptoms
– Minor salivary gland origin : secondarily ulcerated by trauma to the overlying mucosa
23
ONCOCYTOMA

23. GROSS
FEATURES
24
White –gray with focal areas of red-brown
haemorrhage, homogenous in consistency,
distinct intersecting CT septa.
CUT SURFACE
Encapsulated, multinodular/lobulated,
light/mahogany brown
ONCOCYTOMA

24. MICROSCOPIC FINDINGS
25
ONCOCYTOMA
Well circumscribed tumour

25. 26
Arrangement in sheets, cords or nests
forming an alveolar or organoid pattern
ONCOCYTOMA
Groups of oncocytes supported by
numerous thin fiborous connective
tissue septa

26. 27
ONCOCYTOMA
Large, well-defined,
polyhedral or round cell,
brightly eosinophilic
cytoplasm, prominent
granularity
Closely adherent with
distinct cellular boundaries
Centrally located nucleus
(small &
hyperchromatic/large &
vesiculated with prominent
nucleoli
Increased cellular atypia, nuclear
hyperchromatism, pleomorphism
Absence of infiltration

27. SPECIAL STAINS AND IHC
28
ONCOCYTOMA
PTAH: deep blue colour
*Luxol-fast
blue reaction
*Bensley’s
aniline-acid
fusion
IHC :
Positive for cytokeratin

28. Clinical behaviour and Treatment
• Surgical excision
– Partial parotidectomy with facial nerve preservation
– Complete glandectomy (submandibular gland)
– Minor salivary gland : local excision (along with margin of tumour free tissue)
• Low rate of recurrence
29
ONCOCYTOMA

29. 2. ONCOCYTOSIS
• Metaplastic, sometimes hyperplastic
developmental/transformational process
• Focal replacement of normal glandular tissue
• Enlarged eosinophilic epithelial cells with granular
cytoplasm
30

30. • Seen in older people (mean age : 63.9 years)
• Sign of aging
• Majority of cases : parotid
• Incidental finding : diffuse hyperplastic oncocytosis
• Florid : swelling suggesting neoplasm
31

31. Microscopic features
32
Scattered foci of enlarged, eosinophilic
epithelial cells
Solitary focus of metaplastic oncocytes
ONCOCYTOSIS

32. Microscopic features
33
Oncocytosis (clear cell type)
Diffuse hyperplastic oncocytosis
ONCOCYTOSIS

33. 3. ONCOCYTIC CARCINOMA
• Malignant epithelial salivary gland tumour
• Oncocytes demonstrate histopathological features of
– Adenocarcinoma
– Clinical evidence of metastasis
– Or both
34
Least common of all
salivary gland
malignancies

34. CLINICAL FEATURES
Site
Parotid gland
Single case in
submandibular gland,
palate and buccal
mucosa each Age
elder population
Avg. Age : 64 years Male predilection
Cause
Transformation of a
long-standing benign
oncocytoma
May arise de novo
35
ONCOCYTIC CARCINOMA
- Clinically indistinguishable from
benign salivary gland neoplasms
- Infiltration by the tumour causing
facial nerve pain, paresthesia or
paralysis

35. MICROSCOPIC FEATURES(DIAGNOSTIC
CRITERIA)
36
ONCOCYTIC CARCINOMA
1. Recognition of oncocytic neoplasm

36. 37
ONCOCYTIC CARCINOMA
2. Observation of malignant clinical and/or
histopathologic behaviour
Overwhelming evidence of nuclear and cellular pleomorphism and markedly increased or
abnormal mitotic figures

37. 38
3. Invasion into surrounding structures
ONCOCYTIC CARCINOMA

38. 39
- Peri-neural invasion by the tumor and cohesive clusters of neoplastic cells
- High magnification image demonstrating oncocytic cells with abundant and finely granular
cytoplasm and moderately pleomorphic nuclei located centrally or peripherally

39. 40
cervical specimen
showing metastatic
tumor infiltration
by oncocytic cells
(1) local LN mets;
(2) distant mets;
(3) peri-neural,
vascular/lymphatic
invasion;
(4) frequent
mitoses and
cellular
pleomorphism with
extensive invasion,
destruction of
adjacent structures.

40. DIFFERENTIAL DIAGNOSIS
41
ONCOCYTIC CARCINOMA
Recurrent benign oncocytoma Prior history of excision
Salivary duct carcinoma Intensity of PTAH staining reduced
Acinic cell carcinoma Prominent zymogen granularity with PAS
Mucoepidermoid carcinoma Intracytoplasmic mucin with mucicarmine
Carcinoma ex mixed tumours Presence of myoepithelial, chondroid, osseous or
myxomatous features

41. 42
ONCOCYTIC CARCINOMA
SALIVARY DUCT CARCINOMA ACINIC CELL CARCINOMA

42. 43
ONCOCYTIC CARCINOMA
Mucoepidermoid carcinoma Carcinoma ex pleomorphic adenoma

43. Clinical behaviour and Treatment
• Regional lymph node metastasis/distant organs noted
• Recurrence rate :33% with multiple recurrences
• Surgical excision (total parotidectomy with preservation of facial nerve)
• Prophylactic radical neck dissection
• Radiatian therapy : not favourable
44
ONCOCYTIC CARCINOMA

44. CLEAR CELL ONCOCYTOMA
• Clear cells : 11% of oncocytomas
• Dominant / partial component
• Oncocytes replaced by clear cells
• Retain round central nuclei and pink granularity in
cytoplasm
• Cytoplasmic clearing : glycogen accumulation,
displacing mitochondria peripherally
45

45. 46
Cytoplasm of clear cells strongly positive with PAS
reaction
Electron micrographs: Large quantities of cytoplasmic
glycogen

46. BENIGN LESIONS SHOWING
ONCOCYTIC METAPLASIA
(WARTHIN’S TUMOUR, PLEOMORPHIC
ADENOMA)
47

47. HYBRID ONCOCYTOMA
(WARTHIN’S TUMOUR)
• Papillary cystadenoma lymphomatosum (PCL)
• Benign neoplastic process
48

48. CLINICAL FEATURES
49
Site
Parotid gland
Submandibular gland
Minor salivary glands
(ectopic) : palate, lower
lip, buccal mucosa
tongue, larynx,
maxillary sinus
Age
elderly
Fifth and sixth decades
Male to female ratio 5:1
More in whites
Cause
Smoking
EBV
Radiation
WARTHIN’S TUMOUR

49. CLINICAL
PRESENTATION
• Bilateral presentation
• Solitary, nodular, slowly enlarging swelling
• Superficially located PCLs : facial asymmetry
(lymph nodes in superficial and medial portions)
• Location : inferior pole of parotid next to angle of mandible
• 2 to 3 cms in size at the time of diagnosis
50
Moderately firm to
fluctuant
Asymptomatic
Pain,pressure,rapid
increase in size : rare
WARTHIN’S TUMOUR

50. FINE NEEDLE ASPIRATION
CYTOLOGY
51
Cystic fluid, lymphocytes and clumps of
oncocytic epithelial cells
Lymphocytic component : evenly scattered, amorphous
with some cellular debris or mucoid material
Atypical epithelial features : PCL tumours exhibiting cystic
degeneration, necrosis, or squamous metaplasia
WARTHIN’S TUMOUR

51. GROSS PATHOLOGICAL
FEATURES
52
Spheric or oval mass, covered by a
thin, tough capsule (intact)
Smooth red-grey lobulated surface
WARTHIN’S TUMOUR

52. 53
Single large cystic space : fluctuant in
consistency
Solid tumour with multiple cystic spaces :
firm and rubbery in consistency
WARTHIN’S TUMOUR

53. MICROSCOPIC
FEATURES
54
Combination of lymphoid matrix and papillations of
eosinophilic epithelial cells forming cystic spaces
Epithelial cells : two cell layers of uniform rows
Tall columnar cells: approximate cystic space, darkly stained
pyknotic nuclei centrally placed near the luminal space
Inner layer of cuboidal and polygonal cells containing nuclei with
prominent nucleoli
WARTHIN’S TUMOUR

54. 55
Epithelial cells separated from lymphoid
stroma by a thin basement membrane
Reactive lymphoid component with
germinal centres
WARTHIN’S TUMO

55. HISTOLOGICAL VARIANTS
56
ONCOCYTOSIS : sheets and nests of
disorganized oncocytic cells showing loss of
papillary formation
SQUAMOUS METAPLASIA : flattened
luminal cells with loss of columnar cells
WARTHIN’S TUMOUR

56. DIFFERENTIAL DIAGNOSIS
58
WARTHIN’S
TUMOUR
ABSENCE OF LYMPHOID STROMA
PAPILLARY
CYSTADENOMA
WARTHIN’S TUMOUR

57. TREATMENT AND PROGNOSIS
• Surgical removal : two theories
– Tumour enucleation with resection of minimal amount of surrounding tissue
– More aggressive superficial parotidectomy
• Easily removed with minimal loss of glandular function
• Facial nerve preserved
• Radiation therapy
– Reduces tumour mass
– Does not eradicate tumour
– Not recommended
• Recurrence rates difficult to assess : multifocal nature
59
WARTHIN’S TUMOUR

58. PLEOMORPHIC ADENOMA
• Most common salivary gland tumour
• Characterized by histo-morphological diversity
– Myxoid
– Chondroid
– Osseous
– Hyalinized and squamous areas
60
Rare
presentation :
presence of
oncocytes

59. MICROSCOPIC FEATURES
61
PLEOMORPHIC ADENOMA
Oval to polygonal oncocytic cells with dark
granular eosinophilic cytoplasm and a hyalinized
stroma
Two cell populations; clear cells showing
oncocytic appearance and non-oncocytic cells

60. 62
PLEOMORPHIC ADENOMA
Immunohistochemically positive for anti-mitochondrial antibody

61. MALIGNANT LESIONS
EXHIBITING ONCOCYTES
(Muco-epidermoid Carcinoma And
Acinic Cell Carcinoma)
64

62. MUCOEPIDERMOID CARCINOMA
• Most common malignant salivary gland tumour
• Oncocytic variant of MEC : less frequently encountered
65

63. MICROSCOPIC FEATURES
66
LOW-GRADE MEC WITH ONCOCYTIC
METAPLASIA
MUCOEPIDERMOID CARCINOMA
ONCOCYTOMA

64. ACINIC CELL CARCINOMA
• “A malignant epithelial neoplasm of salivary glands in which at least some of the neoplastic
cells demonstrate serous acinar cell differentiation, which is characterized by cytoplasmic
zymogen secretory granules. Salivary ductal cells are also a component of this neoplasm.”
WHO 2005
67

65. CLINICAL FEATURES
68
Site
Parotid gland (most
common)
Age
Wide age range
Children as young as
few years old to elderly
individuals
female patients
Cause
CLINICALLY: SLOW GROWING,
PAINLESS UNFIXED Mass in the
parotid region with rarely
encountered FACIAL NERVE
PALSY
ACINIC CELL CARCINOMA

66. FINE NEEDLE ASPIRATION
CYTOLOGY
69
THE CYTOPLASMIC VACUOLES AND ZYMOGEN GRANULES are the key to the
cytologic diagnosis of acinic cell carcinoma

67. MICROSCOPIC FEATURES
70
Large, round to polygonal cells, basophilic to
amphophilic cytoplasm, dark staining cytoplasmic
granules
Nuclei : round, eccentrically located with fine to
coarse granular chromatin
ACINIC CELL CARCINOMA

68. 71
Vacuolated cells : peculiar cells about the size of
acinar cells with eccentrically placed nucleus.
Cytoplasmic compartment is punctated by clear
vacuoles that occupy most of the cytoplasm
ACINIC CELL CARCINOMA

69. DIFFERENTIAL DIAGNOSIS
72
Oncocytoma
V/S
Acinic cell carcinoma showing oncocytes
ACINIC CELL CARCINOMA

70. DIFFERENTIAL DIAGNOSIS
73
Oncocytoma Acinic Cell Carcinoma
Densly granular to waxy-appearing
cytoplasm without vacuoles
Acinic cells : delicate cytoplasm with
small vacuoles
Mitochondria (PTAH +) Zymogen granules (PAS+)

71. SUMMARY
75

72. FEATURES OF AN ONCOCYTIC
LESIONS
1. Cytoplasmic mitochondria
2. May form a primary tumor (e.g., oncocytoma)
3. May be a metaplastic process (e.g., oncocytosis)
4. Can affect salivary gland neoplasms (e.g., pleomorphic adenoma)
76

73. SALIVARY GLAND FNA
77
NORMAL TISSUE
ABSENT
CYTOPLASMIC VACUOLES
PRESENT
ABSENT
• ACINIC CELL CARCINOMA
• METASTASIS
• ONCOCYTOMA
• WARTHIN TUMOUR
• MEC
•ONCOCYTIC CARCINOMA
• METASTASIS

74. CONCLUSION
 Salivary glands exhibit a wide range of benign and neoplastic lesions that can have
oncocytic or oncocyte like-features.
 Although oncocytic changes are predominantly age-related or seen in benign lesions, similar
change may be occasionally encountered in certain malignant lesions as well.
 Hence a meticulous approach is required for accurate diagnosis.
79

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80

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81

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