Discussion+ Plus+MDSC+Summary

8/2/2019 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/

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