Skin tumors…examples The main risk factor for the tumors in boxes is sun exposure (among others) and lightly pigmented individuals are more at risk Remember xeroderma pigmentosum patients and their tendency for malignant skin tumors Epidermal tumors Adnexal tumors Melanocytic tumors Dermal tumors SCC in situ -Squamous cell carcinoma (SCC) -Basal cell carcinoma (BCC) Melanoma (the benign counterpart is nevus...epidermal, intradermal, junctional or compound) Actinic keratosis Basal cell layer atypia (dysplasia) with risk to transform into SCC in situ & SCC (just a risk…not always)

Invasive SCC A nodule or non-healing ulcer Any site on the face and others, especially sun-exposed

BCC The most common cancer worldwide Sometimes ulcerated: rodent ulcer …due to telangiectatic vessels in the dermis Commonly found on the face above a line drawn from the angle of the mouth to the lobe of the ear Most basal cell carcinomas have mutations that lead to unbridled Hedgehog signaling (like mutations of the tumor suppressor PTCH) Non-metastasizing but locally destructive and occasionally can be disfiguring What is Gorlin syndrome?

*Melanoma: -Asymmetry -Border irregularity -Variation in color -Large size *Remember in melanoma pathogenesis: Radial growth (inside the epidermis) then vertical growth then metastasis

Features of melanoma

The main 4 types of melanoma Sun-exposed areas The main 4 types of melanoma

Intradermal nevus (the most common type of nevus) Epithelioid benign cells maturation In melanoma: in addition to atypia and deep and epidermal invasion, the maturation is lost Remember that giant congenital hairy nevus and dysplastic nevus carry some risk of transformation into melanoma Lymphocyte-like benign cells Spindle benign cells Visit https://emedicine.medscape.com/article/1962932-overview#a7 for references

(Benign) (Malignant) (Benign) (Malignant)

The most common soft tissue tumor of adulthood *Lipoma: -well-circumscribed -homogenous -fatty cut surface -soft The most common soft tissue tumor of adulthood visit https://grosspathology-sites.uchicago.edu/page/lipoma for references …usually arises in the subcutis of the proximal extremities and trunk, most frequently during middle adulthood

Bland-looking nuclei…small and at the periphery Mature fatty tissue *Lipoma Bland-looking nuclei…small and at the periphery Large one fat vacuole Visit http://www.pathologyoutlines.com/topic/softtissueadiposelipoma.html for references

Liposarcoma Large Firm to hard Fleshy Heterogenous cut surface Fixed to the skin and may ulcerate One of the most common sarcomas of adulthood Liposarcoma …mainly in people in their 50s to 60s in the deep soft tissues of the proximal extremities and in the retroperitoneum Note the enlarged nuclei with hyperchromasia and marked pleomorphism

Bland-looking spindle nuclei that infiltrates surrounding structures such as muscle Skeletal muscle fiber Fibromatosis

Same as previous slide

*An example of superficial fibromatosis *Another example of superficial fibromatosis is peyronie's disease of the penis (curved, painful erections) *Desmoid tumor is an example of deep fibromatosis …abdominal wall is most common …may follow pregnancy

UPS (undifferentiated pleomorphic sarcoma) an abnormal mitosis a bizarre cell UPS (undifferentiated pleomorphic sarcoma) …as its name indicates -The most common sarcoma in adults -Most arise in the deep soft tissues of the extremity, especially the thigh of middle aged or older adults

Bone tumors…examples Bone-forming tumors Cartilage-forming tumors Tumors of unknown origin Metastases ABC Osteosarcoma (malignant) Osteochondroma (benign) Chondrosarcoma (malignant) Ewing sarcoma family tumors (malignant) Giant cell tumor (benign) Chondroma/enchondroma (benign) = “secondary bone tumors” ..the most common malignant bone tumor Primary bone tumors Aneurysmal bone cyst: -consists of multiloculated blood-filled cystic spaces -can be a 1ry tumor or a reaction to certain bone tumors

Osteochondroma = “Exostosis” -The most common benign bone tumor -85%: solitary (late adolescence and early adulthood) …the remainder: multiple hereditary exostosis syndrome -Most commonly: metaphysis of long bones especially around the knee -slow-growing masses -can be painful if they impinge on a nerve or if the stalk is fractured -In many cases they are detected incidentally -Osteochondromas usually stop growing at the time of growth plate closure Cartilage cap that remained after ossification of the part proximal to original bone The cartilage cap resembles a disorganized growth plate Stalk with a cavity continuous with original bone cavity Unremarkable bone & bone marrow 5-20% progress to chondrosarcoma

Chondroma/Enchondroma If central (medullary) *Age: 20s-50s *Hand and foot bones are most common *Mainly metaphysis Ollier disease and Maffucci syndrome …multiple enchondromas …more risk for progressing to chondrosarcoma

Osteosarcoma Characteristic, but not only here Due to breaking through cortex and periosteum lifting, a reactive bone formed a triangle (Codman triangle) Lace-like osteoid is characteristic Osteoid directly formed by malignant cells...may be mineralized later Pleomorphic cells and abnormal mitoses

Osteosarcoma *The most common site: around the knee *The most common primary malignant tumor of bone, exclusive of myeloma and lymphoma *The most common site: around the knee *Bimodal age distribution: …mostly: <20 year old …a smaller ratio: older adults (commonly due to an underlying condition) *Males more than females …typically: painful, progressively enlarging masses …sometimes a sudden fracture of the bone is the first symptom *Remember that the fracture due to trivial trauma because of bone disease is called: pathological fracture *Common genes affected: -RB…70% of sporadic cases -TP53 -INK4a…encodes 2 tumor suppressors (p16 (inhibitor of cyclin-dependent kinases) & p14 (augments p53 function)) -MDM2 (inhibitor of p53) & CDK4 (inhibitor of RB) *Hematogenous spread…especially to the lung *Recurrent, metastatic and secondary osteosarcomas have worse prognosis Chemotherapy + Surgery

Chondrosarcoma *The most common subtype is: conventional chondrosarcoma *Mostly central (intramedullary) *Axial skeleton more, especially the pelvis *The 2nd most common malignant matrix-producing tumor *Usually as a painful, progressively enlarging masse

Ewing sarcoma family tumors …one of the small round blue cell tumors Ewing sarcoma family tumors *Recently, Ewing sarcoma and primitive neuroectodermal tumor (PNET) have been unified into a single category: the Ewing sarcoma family tumors (ESFT) *The second most common group of bone sarcomas in children …a striking predilection for whites; blacks and Asians are rarely afflicted …mainly diaphysis of long bones, especially femur EWS gene (on chromosome 22) rearrangements *The characteristic periosteal reaction produces layers of reactive bone deposited in an onion-skin fashion

Giant cell tumor (= “Osteoclastoma”) *Age: 20s-40s *Rare *Benign but locally aggressive …mainly the epiphysis of long bones *The background mononuclear cells are the neoplastic cells here

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