Clear Cell Lesions

Dr. SHUBHANGI MHASKE

Prof and Head
People’s College Of Dental Sciences &
Research Centre,Bhopal
 CONTENT
Introduction
Mechanism of clear cell formation
Classification
Odontogenic cysts and odontogenic tumors
CCL
Salivary Gland CCL/ CCT
Keratinocytic tumors/ CCL
Metastatic and other lesions
Diagnostic algorithm
 Clear cells are characterized by
their translucent appearance
under microscopy, primarily due
to the accumulation of
Intracellular substances such as
glycogen, lipids, or mucin.
Introduction Their presence and distribution
are crucial for diagnosing and
understanding various aggressive
pathological lesions..
 Clear cell
A cell especially a
neoplastic finely
vacuolated with central
dark nuclei, containing
abundant glycogen or
other material that is not
stained by hematoxylin or
eosin so that the
cytoplasm appears clear
histologically.
Types of Clear Cells

1. Physiologic Clear Cells

Non Keratinocytes
Pigment producing cells (melanocytes)
Langerhans cells
Merkel cell
Cell rests of Malassez (Odontogenic)
2. Adipose cells
Pathologic Clear Cells
Mucous/
Benign orAcinar Cells tumour of
malignant
Sebacceous Adnexa Cells Melanocytic Or
Epithelial, Mesenchymal,
Hematopoietic Derivation
 Optical clearance of neoplastic cells in the
H and E section can be due to

artifactual changes,
loss of cell organelles
Mechanism and/or accumulation of various substances, such as
glycogen, lipids, mucopolysaccharides,
of Clearing immature zymogen granules and water in the
cytoplasm.

The cytoplasmic clearance in the clear cell

variant of SCC of skin is due to hydropic
degeneration and accumulation of fluid,

Clear cell differentiation may also result from

different clonal evolution within the tumour.
 Clear cell odontogenic lesions
Odontogenic cystsa. Gingival cyst of
adultsb. Lateral periodontal cystc.
Clear cell calcifying odontogenic cyst
Odontogenic tumorsa. Clear cell
odontogenic carcinomab. Clear cell
odontogenic ghost cell tumorc. Clear
Classificatio cell calcifying epithelial odontogenic
tumor
n Clear cell salivary gland tumorsa.
Clear cell myoepitheliomab. Clear cell
oncocytomac. Clear cell mucoepidermoid
carcinoma d. Clear cell acinic cell
carcinomae. Clear cell myoepithelial
carcinoma
f.Epithelial myoepithelial carcinoma
g. Hyalinizing clear cell carcinoma
 Adipocytic tumorsa. Lipomab.
Liposarcoma
Clear cell tumors arising from skin
adnexa
Trichilemmoma
Clear cell acanthoma
Classificatio Sebaceousadenoma
Sebaceous carcinoma
n Syringomas
Eccrine spiradenoma
Clear cell hidradenoma
Miscellaneous clear cell conditionsa.
Storage diseases—Hurler’s syndrome b.
Viral lesions—koilocytesc.
Alveolarsoftpartsarcomad. Paraganglioma
 .Clear cell metastatic tumors include
carcinomas arising from a. Kidneyb.
Liverc. Thyroidd. Prostatee. Large bowel
Clear cell keratinocytic tumorsa. Clear
cell variant of squamous cell carcinoma b.
Clear cell variant of basal cell carcinoma
Classificatio Clear cell melanocytic tumors
a. Balloon cell nevusb. Balloon cell
n melanoma
Clear cell bone and cartilagenous
tumorsa. Clear cell chondrosarcomab.
Clear cell osteosarcoma
 Clear cell Odontogenic lesions

Odontogenic cysts
Odontogenic
tumors
 Lateral PDL cyst
(LPC)

Clear cell Gingival cyst of

odontogenic Adults (GCA)
cysts

Calcifying Epithelial
Odontogenic cyst
(CEOC)
Lateral Periodontal Cyst (LPC)
Cell rests of
Malassez

Copyright © de Carvalho LF, Lima CF, Cabral LA, Brandão AA,

Almeida JD.J Oral Maxillofac Res 2010 (Oct-Dec);1(4):e5.
doi:10.5037/jomr.2010.1405
Gingival Cyst Of Adults
(GCA)

https://doi.org/
10.1155/2017/4346130
 Calcifying Odontogenic
Cyst (CCOC)

Ide, F., Muramatsu, T., Miyazaki, Y. et al. Calcifying Odontogenic Cyst Showing a Varied Epithelial Lining:
An Additional Case with Implications for the Divergent Differentiation Capacity of the Cyst
Epithelium. Head and Neck Pathol 13, 251–254 (2019). https://doi.org/10.1007/s12105-018-0899-1
 Clear Cell Odontogenic tumors

1. Clear cell variant of calcifying

epithelial odontogenic tumor
(CCCEOT),
2. Clear cell odontogenic carcinoma
(CCOCa)

3.
Clear cell odontogenic ghost cell
tumor (CCOGCT)
Clear Cell Odontogenic tumors

Clear cell variant of

calcifying epithelial
odontogenic tumor
(CCCEOT),

IHC Marker-
CK14, CK19,
CD138, AE1/ AE3

Sahni, Priya & Nayak, Meghanand & Singhvi, Abhishek & Sharma, Jayanti. (2012).
Clear cell calcifying epithelial odontogenic (Pindborg) tumor involving the maxillary
sinus: A case report and review of literature. Journal of oral and maxillofacial
pathology : JOMFP. 16. 454-9. 10.4103/0973-029X.102520.
Clear cell odontogenic carcinoma (CCOCa)

High-power view of clear cell odontogenic carcinoma

showing a biphasic pattern. a Cells with clear
cytoplasm. b Cells with light eosinophilic cytoplasm.
(Hematoxylin and eosin, ×400)
IHC Marker-
CK 19, p63, CK56
Santana, T., de Andrade, F.L., de Sousa Melo, M.C. et al. Clear Cell Odontogenic Carcinoma Harboring the EWSR1–ATF1 Fusion Gene: Report
of a Rare Case. Head and Neck Pathol 14, 847–851 (2020). https://doi.org/10.1007/s12105-019-01103-4
Upadhyay, S., Bhavthankar, J., Mandale, M.S., & Barewad, B. (2019). Clear cell odontogenic carcinoma: Case report
of a deceptive pathology. Journal of Oral and Maxillofacial Pathology : JOMFP, 23, 140 - 143.
 C
K
1
9

Clear cell odontogenic carcinoma exhibiting focal immunopositivity for CK7 (a), CK14 (b), CK19 (c) and p63 (d)
(immunohistochemistry, ×400). The lesion was positive for PAS (e) and negative for PAS-diastase (f)
 Clear cell odontogenic ghost cell
tumor (CCOGCT).

The neoplastic tumor in an epithelial Ghost cell change may be due to

lining showing a basal layer of columnar coagulative necrosis, accumulation of
cells arranged in a palisading pattern with enamel protein, aberrant
cells resembling stellate reticulum, with keratinization of odontogenic
clusters of ghost cells epithelium and these cells may calcify IHC Marker-
CK19, AE1/
AE3

Jia MQ, Jia J, Wang L, Zou HX. Ghost cell odontogenic carcinoma of the jaws: Report of two cases and a

literature review. World J Clin Cases 2019; 7(3): 357-365 [PMID: 30746377 DOI:
 Clear Cell Salivary Gland
Tumors
a. Clear cell b. Clear cell c. Clear cell
oncocytoma mucoepiderm acinic cell
oid carcinoma carcinoma

d. Clear cell e. Epithelial f. Hyalinizing

myoepithelial myoepithelial clear cell
carcinoma carcinoma carcinoma
Mechanism of clear cell formation
in SGT
Reflection of peculiar functional
states of the tumour cells as
reported especially in salivary gland
tumours;

scarcity of organelles in cells of salivary

ducts which give them an empty
appearance;
intracellular accumulation of various
substances such as glycogen in
myoepithelial cells,
accumulation of mucin in mucous cells,
lipids in sebaceous cells,
 Clear Cell Oncocytoma

Oncocytoma presents at age

of approximately 65 years
mostly in parotid.
May be well-circumscribed or
multinodular,
Comprised almost exclusively
of one cell type (oncocyte),
and exhibit a variety of
architectural patterns (nests,
trabeculae, sheets, and duct-
like configurations).

IHC Marker-
p63,
Vimentin,CD10

Kumar, Sunil Bylappa et al. “Oncocytoma Parotid Gland: A Case Report and Brief Review of
Literature.” International Journal of Head and Neck Surgery 5 (2014): 25-27.
 Clear Cell Myoepithelial Carcinoma
A 60-year-old woman had a previous
history of resected pleomorphic
adenoma in the left parotid gland in
another hospital, 13 years before.
She presented with a nodule again in
the same location, 2 cm large, fixed,
and firm in consistency.
The patient was diagnosed with the
clinical suspicion of recurring
pleomorphic adenoma.
The lesion was removed.
Histopathology revealed CCMC.

IHC Marker-
Calponin

1. Alos L, Castillo P. Clear-Cell Myoepithelial Carcinoma of the Parotid Gland. In: Franchi A, ed. Pearls
and Pitfalls in Head and Neck Pathology. Cambridge University Press; 2019:49-51.
Clear Cell Mucoepidermoid Carcinoma

Focal clear cell changes can occur due to accumulation of glycogen

Mucous cells embedded in epidermoid cell nests or lining cystic spaces
IHC Marker-
WNT-1, BCL2, Calponin, E Cadherin,
Vimentin
Clear Cell Mucoepidermoid Carcinoma

Augustine, D., Sekar, B., & Murali, S. (2013). Clear cell variant of mucoepidermoid carcinoma – A rare report with special staining. Indian Journal of

Dentistry, 4(4), 215–218. doi:10.1016/j.ijd.2012.10.010

Clear Cell Mucoepidermoid Carcinoma -PAS Stain

Intracytoplasmic (diastase )PAS-D-positive

globules.

S. Afr. dent. j. vol.73 n.2 Johannesburg Mar.

2018
 Mucicarmine Stain

Serrano-Arévalo ML, Mosqueda-Taylor A, Domínguez-Malagón H, Mi- chal M. Mammary Analogue

Secretory Carcinoma (MASC) of salivary gland in four Mexican patients. Med Oral Patol Oral Cir
Bucal. 2015 Jan1;20 (1):e23-9.
Clear cell acinic cell carcinoma

Acinic cell carcinoma showing clear cells

arranged in acinar pattern.
 Clear Cell Myoepithelial Carcinoma
Nodules often have a hypocellular
center with hyalinized stroma or bland
necrosis surrounded by a hypercellular
peripheral zone
Tumor necrosis can be seen within the
hypercellular central zone of a tumor
nodule
Composed (near) entirely of
myoepithelial cells showing various
cytologic features, including clear cell,
epithelioid, plasmacytoid or spindle cell
morphology
Hyalinized, myxoid or myxochondroid
stroma may be seen in myoepithelial
carcinoma de novo and ex PA
Common architectural patterns include
solid, trabeculae, cords, nests and
single cells

https://www.pathologyoutlines.com/topic/salivaryglandsmyoepithelialcarcinoma.html
 Epithelial Myoepithelial Carcinoma

Characterized by biphasic architecture consisting of cuboidal ductal cells

(black arrow) and myoepithelial cells (red arrow) (200×).

Wu, Haohao & Zhang, Fangbiao & Peng, Jiahui & Wu, Zhiju & Zhang, Xiangyan & Wu, Xingzhen. (2022). Epithelial–Myoepithelial
Carcinoma of the Esophagus: A Case Report. Frontiers in Surgery. 9. 942019. 10.3389/fsurg.2022.942019.
 Hyalinizing Clear Cell Carcinoma

Hyalinizing clear cell carcinoma with characteristic hyalinizing

stroma

O'Sullivan-Mejia, E & Massey, H & Faquin, William & Powers, Celeste. (2009). Hyalinizing Clear Cell Carcinoma: Report of Eight Cases
and a Review of Literature. Head and neck pathology. 3. 179-85. 10.1007/s12105-009-0124-3.
Algorithm For Clear Cell Salivary Gland
Tumors

Rodríguez MS, Reija MF, Rodilla IG. Primary clear cell carcinoma of parotid gland: Case report
and review of literature. J Oral Maxillofac Pathol. 2013 Jan;17(1):101-5. doi: 10.4103/0973-
029X.110692. PMID: 23798840; PMCID: PMC3687162.
 Clear Cell
Keratinocytic
Tumors

Squamous cell carcinoma-mostly

skin tumors present as CCL
Clear Cell Keratinocytic Tumors

Clear cell variant of Clear cell variant of

basal cell carcinoma squamous cell
carcinoma

Cytokeratin , AE1/AE3, – EMA, CK8,

CK18
 Clear Cell
Melanocytic
Tumors Balloon cell nevus

SOX1
Balloon cell melanoma
0
Skin And Adipose Clear
Cell Lesions
 Clear cell tumors arising from skin
adnex
a. Trichilemmoma

b. Clear cell acanthoma

Clear Cell
c. Sebaceous adenoma
Tumors of
d. Sebaceous carcinoma
Skin Adnexa
e. Syringomas

f. Eccrine spiradenoma

g. Clear cell hidradenoma

 Adipocytic Tumors
Lipoma And Liposarcoma

'Lipoma-like' well-differentiated liposarcoma

scattered fibrous septa containing hyperchromatic spindle cells

MDM2 and CDK4 using

FISH
Clear Cell Bone and
Cartilaginous Tumors
 Clear Cell
Chondrosarcom
a And Clear Cell
Osteosarcoma

HIF-2α
protein
Miscellaneous Clear cell conditions

a. Storage diseases—Hurler’s
syndrome

b. Viral lesions—koilocytes

c. Alveolar soft part sarcoma d.

Paraganglioma
Uncommon lesions- Metastatic Lesions

Clear cell metastatic tumors

include carcinomas arising from

a. Kidney
b. Liver
c. Thyroid
d. Prostate
e. Large bowel
Diagnostic work up
Diagnostic Challenges -clear cell
tumors

varied histological
appearance,

Potential for mimicry

with other conditions,
and

diverse clinical
behavior.
A multidisciplinary approach involving
Histopathology,

Molecular analysis,

Imaging,

Clinical correlation is essential for-

Accurate diagnosis,
Prognostication, and
Management of patients with clear
cell tumors.
Flowchart of Diagnostic Process
Salivary gland Odontogenic Squamous cell
lesion Tumors/Cysts Carcinoma

Clinical Clinical and Histopathologica

corelation- radiological l diagnosis by
Location- Diagnosis H&E (gold std)
Parotid/Palate Intraooseus Diagnosis by
etc lesions arising exclusion of
Slow growing from salivary gland
PAS stain Odontogenic tumors and
/mucicarmine Apparatus Odontogenic
positive for Odontogenic tumors/Cyst
Acinic Cell and tumor markers- IHC-cytokeratins
MEC IHC may /may
SMA – not be required
Myoepithelial Ca
and Hyalinising
clear cell Ca.
 To Summarize…

Clear cells are a focal population in majority of

tumors/ lesions
Biphasic patterns may be seen eg. Odontogenic
Carcinoma
Conventional Histopathology and clinical correlation
is important for diagnosis
Prognosis of clear cell tumors based on type and
stage.
 Conclusion
The clear cell tumors and conditions of the head and neck are a
heterogenous group with a common entity—the ‘clear cells’. The
distinction between these tumors is confounding due to their similar
histological appearance.
The biological behavior may range from indolent to aggressive.

But in most cases the presence of clear cells may prove to be a sign
of increased tumor aggressiveness.

Thus, their appropriate diagnosis is crucial