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
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
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
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
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
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
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
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
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
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
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
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
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
75. REFERENCES
• Ellis GL, Auclair PL, Gnepp DR. Surgical Pathology of the Salivary Gland. Philadelphia,
W.B. Saunders Company; 1991. p 225-227.
• Dardick I. Oncocytoma and Oncocytic adenocarcinoma In: Colour Atlas/Text of Salivary
Gland Tumour Pathology. Igaku-Shoin Medical Publishers, Tokyo .p. 105-116.
80
76. • Palma SD, Lambros MBK, Savage K, et al. Oncocytic change in pleomorphic adenoma:
molecular evidence in support of an origin in neoplastic cells. Journal of Clinical Pathology.
2007;60(5):492-499.
• Sarode GS, Sarode SC, Patil S, Anil S. Oncocytic Pleomorphic Adenoma of Palatal Salivary
Gland with Macrophages and Giant Cells Associated with Cholesterol Crystals. Clinics and
Practice. 2016;6(4):884.
81
77. • Sheikh El et al. Oncocytic Carcinoma of the Maxillary Sinus (A Case Report). Journal of
Applied Sciences Research, 9(1): 263-270, 2013
• Histology, 5th ed, Michael H. Ross, Wojciech Pawlina
• Brannon RB, Willard CC. Oncocytic mucoepidermoid carcinoma of parotid gland origin. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Dec; 96(6):727-33.
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78. 83
•Bauer, W. H., Bauer, J. D. (1953) Classification of glandular tumours of salivary glands.
Study of 143 cases. Archives of Pathology, 55: 328-346.
•Blanck, C, Eneroth, C. -M., Jakobsson, P. A. (1970) Oncocytoma of the parotid gland.
Neoplasm or nodular hyperplasia? Cancer, 25: 919-925.
•Buxton, R. W., Maxwell, J. H., French, A. J. (1953) Surgical treatment of epithelial
tumours of the parotid gland. Surgery, Gynecology and Obstetrics, 97: 401^4-16.
79. 84
•Ross, C. F. (1976) Malignant oncocytoma ('oxyphilic granular-cell tumour') of parotid
gland. Clinical Oncology, 2: 253-260.
•Schwartz, I. S., Feldman, M. (1969) Diffuse multinodular oncocytoma ('oncocytosis') of
the parotid gland. Cancer, 23: 636-640.
80. 85
•Sehested, M., Barfoed, C, Krogdahl, A., Bretlau, P. (1985) Immunohistochemical
investigation of lysozyme, lactoferrin, al-antitrypsin, a 1-antichymotrypsin and ferritin in
parotid gland tumours. Journal of Oral Pathology, 14: 459—465.
•Sorensen, M., Baunsgaard, P., Frederiksen, P., Haahr, P. A. (1986) Multifocal
adenomatous oncocytic hyperplasia of the parotid gland. Unusual clear cell variant in two
female siblings. Pathology, Research and Practice, 181: 254-257
81. 86
•Caselitz, J., Schulze, I., Seifert, G. (1986) Adenoid cystic carcinoma of the salivary
glands. An immunohistochemical study. Journal of Oral Pathology, 15: 308-318.
•Eneroth, C. M. (1965) Oncocytoma of major salivary glands. Journal of Laryngology
and Otology, 79: 1064-1072.
•Fayemi, A. O., Toker, C. (1974) Malignant oncocytoma of the parotid gland. Archives of
Otolaryngology, 99: 375-376
Notas del editor
Mitochondria
he two strands of mtDNA are differentiated by their nucleotide content, with a guanine-rich strand referred to as the heavy strand (or H-strand) and a cytosine-rich strand referred to as the light strand (or L-strand).
Mahogany : hard reddish-brown timber from a tropical tree, used for furniture
Poorely preserved tissue : acantholysis
Cytoplasm of both cell layers : finely granular and distinctly eosinophilic
Epithelial
