3. Introduction
Oncocyte : Prefix onco- is derived from the Greek word onkoustai, which
means to swell. Means Swollen Cell.
The term ‘Oncocyte’ was first introduced in 1931 by Hamperl.
Oncocytes are epithelial cells which appear as :-
Cells with abundant, granular, eosinophilic cytoplasm having a
central pyknotic nucleus, and ultra structurally packed with
numerous mitochondria of various sizes.
Oncocytes are seen in various organs like :
Salivary glands,
Thyroid,
Lacrimal glands,
Mammary Gland,
Buccal mucosa,
Esophagus and
organs like liver, pancreas, and kidney, etceteras
.
4. In salivary glands, they may be present in a plethora of conditions
ranging from hyperplasia to overtly malignant lesions.
The 4th Edition of WHO Classification of Head and Neck Tumors
addresses the oncocytic lesions of the salivary gland under
headings of
Nodular oncocytic hyperplasia,
Oncocytoma and
Oncocytic carcinoma.
Few Term:
Oncocytic metaplasia is the transformation of ductal and acinar cells to
oncocytes, generally seen after age of 50.
Oncocytosis refers to both the proliferation and the accumulation of
oncocytes within salivary gland tissue and is considered to be a
metaplastic process rather than a neoplastic one.
Introduction
5. Nodular oncocytic hyperplasia is a non neoplastic epithelial lesion,
Seen generally in the parotid, and in the 5th, and 6th decades of
life.
In rare instances, it may involve the submandibular or minor salivary
glands.
It can be an incidental finding in otherwise normal salivary gland tissue,
but it may be extensive enough to produce clinical swelling.
Usually the proliferation is multifocal and nodular, but sometimes the
entire gland can be replaced by oncocytes (diffuse hyperplastic
oncocytosis).
NODULAR ONCOCYTIC HYPERPLASIA (Oncocytosis)
Ref.: Rooper, L. M., Onenerk, M., Siddiqui, M. T., Faquin, W. C., Bishop, J. A., & Ali, S. Z.
(2017). Nodular oncocytic hyperplasia
6. Histopathologic Features
Microscopic examination usually reveals focal nodular collections of
oncocytes within the salivary gland tissue. These enlarged cells are
polyhedral and demonstrate abundant granular, eosinophilic
cytoplasm as a result of the proliferation of mitochondria.
On occasion, these cells may have a clear cytoplasm due to
accumulation of glycogen.
The multifocal nature of the proliferation may be confused with that of a
metastatic tumor, especially when the oncocytes are clear in
appearance.
NODULAR ONCOCYTIC HYPERPLASIA (Oncocytosis)
Ref.: Rooper, L. M., Onenerk, M., Siddiqui, M. T., Faquin, W. C., Bishop, J. A., & Ali, S. Z.
(2017). Nodular oncocytic hyperplasia
7. Surgical resection specimens highlighted
(A) Oncocytic cells with abundant granular eosinophilic cytoplasm and round to
oval nuclei with prominent nucleoli distributed in (B) multiple
unencapsulated nodules separated by normal appearing salivary tissue
(H & E stain, at 40x and 20x magnification respectively).
NODULAR ONCOCYTIC HYPERPLASIA (Oncocytosis)
Ref.: Rooper, L. M., Onenerk, M., Siddiqui, M. T., Faquin, W. C., Bishop, J. A., & Ali, S. Z.
(2017). Nodular oncocytic hyperplasia
8. ONCOCYTOMA (OXYPHILIC ADENOMA)
Oncocytomas are benign epithelial tumors characterized by oncocytes
with eosinophilic granular cytoplasm rich in mitochondria.
Oncocytomas were first described by Jaffé in 1932.
The parotid gland is the most commonly involved organ accounting for
78–84% of salivary gland oncocytomas .
They occur most commonly in their sixth to eighth decades and are
slightly predominant in women.
The tumor appears as a firm, slowly growing, painless mass that rarely
exceeds 4 cm in diameter.
Parotid oncocytomas usually are found in the superficial lobe and are
clinically indistinguishable from other benign tumors.
9. ONCOCYTOMA (OXYPHILIC ADENOMA)
The oncocytoma is usually
a well-circumscribed
tumor that is composed of
sheets of large polyhedral
cells (oncocytes), with
abundant granular,
eosinophilic cytoplasm.
Sometimes these cells
form an alveolar or
glandular pattern.
Little stroma is present, usually in the form of thin fibrovascular septa. An
associated lymphocytic infiltrate may be noted. The granularity of the
cells corresponds to an overabundance of mitochondria.
Oncocytomas may contain variable numbers of cells with a clear cytoplasm. In rare
instances, these clear cells may compose most of the lesion and create
difficulty in distinguishing the tumor from low-grade salivary clear cell
adenocarcinoma or metastatic renal cell carcinoma.
10. The granules of Oncocytes can be identified on light microscopic
examination with a phosphotungstic acid hematoxylin (PTAH) stain. The
cells also contain glycogen, as evidenced by their positive staining with
the periodic acid-Schiff (PAS) technique.
So Special Stain For Oncocytes are
PTAH
PAS
IHC Stains
Antimitochondrial Antibody
CK 5
CK 8
EMA
ONCOCYTOMA (OXYPHILIC ADENOMA)
Differential diagnosis for Oncocytoma may be Oncocytic Carcinoma,
Oncocytic Metaplasia, Oncocytosis, Warthin Tumors, Oncocytoid
artifact(Produced due to electocautry)
11. ONCOCYTIC CARCINOMA
Oncocytic carcinoma is an extremely rare malignancy of salivary gland,
accounting for 11% of all oncocytic salivary gland neoplasm,
0.5% of all epithelial salivary gland malignancies and 0.18% of
all epithelial salivary gland tumors.
Oncocytic carcinoma as describe by WHO as a proliferation of cyto-
morphologically malignant oncocytes with adeno-
carcinomatous architectural phenotypes including
infiltrative qualities, which may arise de novo and also can be
seen in association with a pre-existing oncocytoma.
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
12. Malignant oncocytoma, malignant oxyphilic adenoma and oncocytic
adenocarcinoma have been used synonymously for oncocytic
carcinoma.
The malignant nature of the neoplasm can be recognized by its
morphologic features and infiltrative growth.
Oncocytic differentiation of neoplastic cells was demonstrated by
immunohistochemical positivity for mithochondrial antigen,
keratin, alpha-1-antichymotrypsin. On ultrastructural analysis
numerous mitochondria seemed to fill the cytoplasm.
Other neoplasms that arise from the salivary gland with a granular
cytoplasm are oncocytoma, acinic cell adenocarcinoma and
salivary duct carcinoma.
ONCOCYTIC CARCINOMA
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
13. Imprint cytology of lesion showing cohesive clusters of neoplastic cells with
abundant and finely granular cytoplasm and moderately pleomorphic nuclei located
centrally or peripherally (a: haematoxylin- eosin, × 400).
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
14. Permanent sections revealed a neoplasm that had invaded subcutaneous adipose
tissue (b: haematoxylin- eosin, × 100)
and perineural tissue (c: haematoxylin-eosin, × 200).
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
15. Neoplastic elements with abundant granular eosinophilic cytoplasm, large nuclei
and evident nucleoli, are large, round or polyhedral cells arranged in solid sheets,
islands and cords (d: haematoxylin-eosin, × 400).
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
16. Oncocytic carcinoma can be differentiated from benign oncocytoma by
the presence of a connective tissue capsule in the latter and
oncocytic carcinoma usually shows a greater mitotic activity
and more nuclear pleomorphism
Acinic cell adenocarcinoma can be differentiated from oncocytic
carcinoma since its cytoplasmic granules are amphophilic or
basophilic. Moreover, the patterns of growth in acinic cell
adenocarcinoma can be microcystic or papillary and the
neoplastic elements are negative for mithochondrial antigen.
Salivary duct carcinoma, in contrast to oncocytic carcinoma, forms
duct-like spaces with papillary and cribriform growth and also
shows comedo necrosis .
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
ONCOCYTIC CARCINOMA
17. The non-neoplastic proliferation of a salivary gland, which can mimic
oncocytic carcinoma is oncocytosis. This can be differentiated
from malignant oncocytoma by the presence of variably sized
foci of oncocytic cells within glandular lobules without altering
the normal architecture of the gland.
Primary oncocytic carcinoma of the salivary glands should also be
differentiated from metastatic oncocytic carcinomas to the
salivary glands from a precise clinical history, revealing the
previous primary neoplasm and by specific
immunohistochemical studies.
The prognosis of oncocytic carcinoma in salivary gland is not well
known, because of its rarity. Goode and Corio have reported that
tumours smaller than 2 cm in diameter appeared to have a better
prognosis than those that were larger.
ONCOCYTIC CARCINOMA
Ref: Giordano G, Gabrielli M, Gnetti L, Ferri T. Oncocytic carcinoma of parotid
gland, doi: 10.1186/1477-7819-4-54. PMID: 16923179;
18. WARTHINS TUMOR
Warthins tumor is a benign neoplasm that occurs almost exclusively
in the parotid gland. it represents the second most common benign
parotid tumor.
The pathogenesis of Warthin tumor is uncertain. The traditional
hypothesis suggests that it arises from heterotopic salivary gland
tissue found within parotid lymph nodes. However, researchers
have also suggested that these tumors may develop from a
proliferation of salivary gland ductal epithelium that is associated
with secondary formation of lymphoid tissue.
A number of studies have demonstrated a strong association between the
development of this tumor and smoking. Smokers have an
eightfold greater risk for Warthin tumor than do nonsmokers.
19. The Warthin tumor usually appears as a slowly growing, painless,
nodular mass of the parotid gland.
It may be firm or fluctuant to palpation. The tumor most frequently
occurs in the tail of the parotid near the angle of the mandible,
and it may be noted for many months before the patient seeks a
diagnosis.
One unique feature is the tendency of Warthin tumor to occur bilaterally,
which has been noted in 5% to 17% of reported cases. Most of
these bilateral tumors do not occur simultaneously but are
metachronous.
Warthin tumor most often occurs in older adults, with peak prevalence
in the sixth and seventh decades of life. Most studies show a
decided male predilection by 10:1, due to smoking factors.
WARTHIN TUMOR
20. The cells have abundant,
finely granular
eosinophilic cytoplasm and
are arranged in two
layers. The inner luminal
layer consists of tall
columnar cells with
centrally placed, palisaded,
and slightly hyper-
chromatic nuclei. Beneath
this is a second layer of
cuboidal or polygonal cells
with more vesicular nuclei.
The lining epithelium demonstrates multiple papillary infoldings that protrude into
the cystic spaces. The epithelium is supported by a lymphoid stroma that frequently
shows germinal center formation.
WARTHIN TUMOR
21. WARTHIN TUMOR
The term papillary cystadenoma lymphomatosum is cumbersome,
it accurately describes the salient microscopic features.
The tumor is composed of a mixture of ductal epithelium and a lymphoid
stroma. The epithelium is oncocytic in nature, forming uniform
rows of cells surrounding cystic spaces.
22. Conclusion
Oncocytes are epithelial cells which appear as Cells with abundant,
granular, eosinophilic cytoplasm having a central pyknotic nucleus, and
ultra structurally packed with numerous mitochondria of various sizes
The rarity and heterogeneity of this group of lesions may cause
difficulties in diagnosis. Care should be taken in histological diagnosis
and immunohistochemistry should perform when needed.
