discussion+ plus+mdsc+summary
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Fig 1: Pre-op photograph of patient with ulcerated lesion on lip (arrow). Lip is also somewhat
thickened. Area of surgical incision has been demarcated. The skin of the lips is stratifiedsquamous epithelium
The border between the lips and the surrounding skin is referred to as the vermillion border, or
simply the vermilion. The vertical groove on the upper lip is known as the philtrum.
The skin of the lip, with three to five cellular layers, is very thin compared to typical face skin,
which has up to 16 layers. With light skin color, the lip skin contains fewer melanocytes (cells
which produce melanin pigment , which give skin its color). Because of this, the blood vessels
appear through the skin of the lips, which leads to their notable red coloring. With darker skincolor this effect is less prominent, the skin of the lips contains more melanin and thus is visually
darker. The skin of the lip forms the border between the exterior skin of the face, and the
interior mucous membrane of the inside of the mouth.
The lip skin is not hairy, and does not have sweat glands or sebaceous glands. Therefore it does
not have the usual protection layer of sweat and body oils which keep the skin smooth, inhibit
pathogens, and regulate warmth. For these reasons, the lips dry out faster and become
chapped more easily.
7. Lip Squamous Cell Carcinoma Case Study
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www.medicalhistology.us/twiki/bin/view/Archiv... Remove frame
Case Study:
Clinical Summary: 63 yr old white male had recurrent thickening and scaling of the lower lip
for two years. In recent months it had undergone ulceration (sore on the skin or a mucous
membrane, accompanied by the disintegration of tissue) and progressive enlargement. The
lesion was excised by wedge resection.
Autopsy findings: specimen was triangular in shape; upper part was covered by mucosa and
the lower part by skin. At the junction of the mucosa and skin, there was a 2 x 1.4 cm ovalshaped superficial lesion which was flat, firm and had raised borders. The base was orange.
.
Fig 2: LP of squamous cell carcinoma of
the lip. Note focal ulceration (1) and
tumor infiltration at the vermilion border
(2)
http://www.medicalhistology.us/twiki/bin/view/Archive/A55_keratinized_stratified_squamous_epithelium_liphttp://www.medicalhistology.us/twiki/bin/view/Archive/A55_keratinized_stratified_squamous_epithelium_liphttp://www.medicalhistology.us/twiki/bin/view/Archive/A55_keratinized_stratified_squamous_epithelium_liphttp://www.medicalhistology.us/twiki/bin/view/Archive/A55_keratinized_stratified_squamous_epithelium_liphttp://www.medicalhistology.us/twiki/bin/view/Archive/A55_keratinized_stratified_squamous_epithelium_lip -
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The role of myeloid-derived suppressor cells in promoting the spread of these malignant
tumors:
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid
progenitors, immature granulocytes, macrophages, and dendritic cells at different stages of
differentiation. These cells are of great interest because they have the capacity to suppress
both the cytotoxic activities of natural killer cells, and the adaptive immune response
mediated by CD4+
and CD8+
T cells
Fig 4: LP of well-differentiated squamous cellcarcinoma and inflammatory cell infiltration
The infiltration of tumors by inflammatory
cells encompasses numerous cellular
phenotypes, including macrophages, dendritic
cells (DCs), myeloid derived suppressor cells
(MDSCs), and T cells
MDSCs can interact with T cells, macrophages,
and natural killer cells to create an environment
favorable for tumor progression.
Tumor-induced immunosuppression plays a
key role in tumor evasion of the immune
system.
Fig 3: Large area of ulceration (arrow)
with underlying congestion and
hemorrhage. Area of ulceration is
adjacent to an area of tumor infiltration.
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Fig 5: HP of infiltrating squamous cell
carcinoma and inflammatory cells
Fig 6: HP of well differentiated lip
squamous cell carcinoma. Note
intracytoplasmic keratinization whichgives the cells a glassy appearance. The
focal accumulations of keratinized cells
(structural cells making up the outer
layer of human skin) are called keratin
pearls (arrows)large keratin plaques
surrounded by necrotic cells with
pyknotic nuclei (irreversible
condensation of chromatin in the nucleus
of a cell undergoing programmed cell
death or apoptosis)
Fig 7: HP of poorly differentiated tumor
area. Note spindle shaped cells and
irregular pattern of growth
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Terminology:
Vermillion border of the lip: the normally sharp demarcation between the lip and the adjacen
normal skinwww.medscape.com/.../slideshow/lip-laceration/.
Pyknotic nuclei: irreversible condensation of chromatin in the nucleus of a cell undergoing
programmed cell death or apoptosis
http://www.rndsystems.com/molecule_group.aspx?g=2424&r=1;
http://onlinelibrary.wiley.com/doi/10.1002/jbmr.154/pdf
So if we consider inflammation as the beginning insult then the pathway through to
transformation might look like this:
Pathway:
Pathogen/insult inflammatory response chronic inflammation (cytokines as
well as reactive O2 species) cellular transformation plus MDSCs
MDSCs secrete mutated TGF beta that no longer promotes apoptosis or anti proliferative
characteristics but rather stimulates immune suppression and angiogenesis, by converting
effector T-cells into MDSCs which interfere with MHC response and specific cell immunity
transformed cells divide and cancer has the potential to invade.
Fig 8: Section of muscle tissue from lip
biopsy. Note squamous cell carcinoma
has infiltrated into the muscle tissue.
There are also inflammatory cells within
this area of tumor infiltration
http://www.medscape.com/features/slideshow/lip-laceration/http://www.medscape.com/features/slideshow/lip-laceration/http://www.medscape.com/features/slideshow/lip-laceration/http://www.rndsystems.com/molecule_group.aspx?g=2424&r=1http://www.rndsystems.com/molecule_group.aspx?g=2424&r=1http://onlinelibrary.wiley.com/doi/10.1002/jbmr.154/pdfhttp://onlinelibrary.wiley.com/doi/10.1002/jbmr.154/pdfhttp://onlinelibrary.wiley.com/doi/10.1002/jbmr.154/pdfhttp://www.rndsystems.com/molecule_group.aspx?g=2424&r=1http://www.medscape.com/features/slideshow/lip-laceration/