Classification of Tumours Professor of Pathology Neoplasia 3 Dr. Faten Ghazal Professor of Pathology

Intended Learning Outcomes (ILOs) By the end of this lecture YOU will be able to: Describe pathologic features of some malignant epithelial tumours (carcinoma) & mesenchymal tumours (sarcoma) Define grading and staging Explain their clinical implication

Malignant Epithelial Tumours (Carcinoma) Surface Epithelial Tumours Glandular Epithelial Tumours Squamous Cell Carcinoma Basal Cell Carcinoma Transitional Cell Carcinoma Duct Papillary Carcinoma Adenocarcinoma (Conventional) Mucoid adenocarcinoma Signet ring carcinoma

How can you describe these lesions?

Malignant Epithelial Tumours (Carcinoma) Any Carcinoma: Pathologic Features Gross: An ulcerating, fungating (rising above the surface or protruding or bulging into the lumen of the organ), and/or infiltrating mass having areas of haemorrhage & necrosis Microscopically: Differ according to cell of origin: as masses or sheets of malignant squamous epithelial cells, or masses of malignant transitional epithelial cells with or without papillae formation or as malignant glands or its variants.

Gross Patterns of Carcinoma facing a lumen or a surface Fungating Ulcerating Infiltrating Normal Carcinoma can be fungating, ulcerating & infiltrating mass

Suggest the microscopic type of Carcinoma Case 1 Squamous Cell Carcinoma An ulcerating mass with raised everted edge and necrotic floor This view shows the transition from normal squamous epithelium into invasive carcinoma. Can you tell by the appearance that the SCC “arose” from the squamous epithelium?

Squamous Cell Carcinoma

Squamous Cell Carcinoma A hallmark of well differentiated squamous cell carcinoma is that the nests of invading cells still attempt to make keratin which then gets deposited in the center of the nests, resulting in a keratin "pearl". A “pearl” in a squamous cell carcinoma qualifies it to be “well” differentiated. From the Iowa Collection

Squamous Cell Carcinoma Stratified Squamous Epithelium Masses of malignant squamous epithelial cells Cell nest Well differentiated squamous cell carcinoma

Squamous Cell Carcinoma Well differentiated squamous cell carcinoma Poorly differentiated squamous cell carcinoma

1 2 3 Well differentiated squamous cell carcinoma: More than 50% of masses contain central keratin 2 3 Moderately differentiated squamous cell carcinoma: 25-50% of masses contain keratin Poorly differentiated squamous cell carcinoma: Less than 25% of masses contain central keratin

Squamous Cell Carcinoma Arises from surface squamous epithelium (stratified squamous epithelium) as: skin, larynx, and esophagus or on top of squamous metaplasia for example in bronchi of smokers & in ………..??. Range of differentiation from: well differentiated showing central keratin pearls to poorly differentiated. Grading of the tumour: is based on the 1. cytological differentiation (keratin formation and presence of intercellular bridges) & 2. number of mitotic figures. Urinary Bladder Extended Modular Program

Basal Cell Carcinoma Locally Invasive Epithelial Tumour Case 2 A nearly rounded elevated mass showing central ulceration with elevated rolled in border present at the ala & tip of the nose Common skin cancer (rodent ulcer) Slowly growing tumor. Rarely metastasize Infiltrates deeper structures In the face it occurs above the line drawn from the angle of the mouth to the lobule of the ear (sun exposed area). Arising from basal cells of the epidermis.

Basal Cell Carcinoma What do you observe at the periphery of the masses? Outer columnar cells arranged in a palisade manner Cells show scanty cytoplasm & large oval hyperchromatic nuclei. No central keratin

Basal Cell Carcinoma Microscopic: revealed a skin & tumour tissue covered by stratified squamous epithelium showing focal or central ulceration. The underlying dermis is infiltrated by: irregular masses or islands of basaloid cells having little basophilic cytoplasm & oval to round nuclei. These masses show peripheral palisading (parallel alignment of longitudinal axis) of their nuclei.

Papillary Transitional Cell Carcinoma vascular connective tissue core Urinary Bladder Mass Papillary Transitional Cell Carcinoma A male patient 55 year old complained of haematuria lower abdominal pain for the last 5 months vascular connective tissue core covered by multilayered transitional epithelium showing nuclear atypia as ….

Transitional Cell Carcinoma Urinary Bladder Mass Transitional Cell Carcinoma Extended Modular Program

Malignant Epithelial Tumours Surface Epithelial Tumours Glandular Epithelial Tumours Squamous Cell Carcinoma Basal Cell Carcinoma Transitional Cell Carcinoma Duct Papillary Carcinoma Adenocarcinoma Mucoid adenocarcinoma Signet ring carcinoma

Adenocarcinoma Malignant tumour arising from glandular epithelial tissue is called …. Well-differentiated tumour is formed of: malignant glands separated by connective tissue stroma. Poorly differentiated tumour is formed of: few glands and more masses of malignant epithelial cells

Well Differentiated adenocarcinoma Normal mucosa Desmoplastic stroma Malignant glands: Well Differentiated adenocarcinoma

2. Mucinous Adenocarcinoma: shows extracellular mucin secretion (pools of mucin) in which are embedded glands and individual cells. e.g. in colorectal and breast cancer. 3. Signet Ring Cell Carcinoma: is a type adenocarcinoma where the malignant cells show intracellular mucin giving the appearance of signet ring cells. e.g. gastric carcinoma

Mucinous Adenocarcinoma of Large Intestine Signet ring cells Extracellular mucin

Signet Ring Cell Carcinoma

Classification of Tumours Clinical (Biological) Behaviour = Benign, Malignant & …..? Locally (Invasive) Aggressive Tumours Cell of Origin (Histogenesis) = Epithelial, Mesenchymal or Mixed Tumours

Extended Modular Program A 25 year old male complained of pain around his left knee with limitation of movement. X ray was done and revealed a radiolucent lesion. Biopsy was done. Extended Modular Program

Giant Cell Tumour (Osteoclastoma) Pathologic Fracture Femur Locally Invasive (Aggressive) Tumours Cut Section Tibia Thin shell of bone

Malignant Mesenchymal Tumours (Sarcomas)

Haematopoietic Tissue Leukemias Tissue of Origin (Mesenchymal) Benign Malignant Adipose Tissue Lipoma Liposarcoma Fibrous Tissue Fibroma Fibrosarcoma Cartilage Chondroma Chondrosarcoma Bone Osteoma Osteosarcoma Smooth Muscle Leiomyoma Leiomyosarcoma Skeletal Muscle Rhabdomyoma Rhabdomysarcoma Mesothelium Benign Fibrous T Mesothelioma Blood Vessels Haemangioma Angiosarcoma Meninges Meningioma Invasive Meningioma Lymphoid Tissue No benign Lymphoma Haematopoietic Tissue Leukemias

Malignant Mesenchymal Tumours Pathologic Features Sarcoma Gross: Irregular large infiltrating mass relatively soft in consistency might show areas of haemorrhage and necrosis Microscopically: Tumours vary according to the cell of origin: Liposarcoma, fibrosarcoma, chondrosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma

Malignant Spindle Cell Tumour most probably Leiomyosarcoma Spindle tumor cells: eosinophilic cytoplasm, elongated nuclei, large highly atypical bizzare giant cells

Grossly, What does it look like? Large bizarre lipoblasts Large mass Common sites are the retroperitoneum and thigh occur in middle aged to older adults. Yellowish cut surface and soft in consistency. Large bizarre lipoblasts Liposarcoma Why not Lipoma??

What are the differentiating features of carcinoma (malignant epithelial cells) & sarcoma (malignant mesenchymal cells)?

Differences between Carcinoma and Sarcoma Origin Epithelial tissue Mesenchymal tissue Age More in old More in young Vascularity Less vascular More vascular Rate of growth Less rapid More rapid Cut section Less haemorrhage More haemorrhage Spread Early by lymphatics (?) Early by blood (?) Prognosis Less worse More worse Microscopic Mostly, cells arranged in groups Mostly, cells arranged individually

Malignant Tumours of Melanocytes (Malignant Melanoma) Sites: Skin of face, neck, chest & anal canal. Gross: Variably pigmented nodule, grows rapidly and tends to ulcerate. Microscopic: Malignant melanocytes from basal epidermis containing melanin grows & infiltrates radially in the epidermis and upper dermis and vertically downwards in the deeper dermis

Advanced Malignant Melanoma: vertical growth into dermis Malignant Tumours of Melanocytes (Malignant Melanoma) Advanced Malignant Melanoma: vertical growth into dermis Early Malignant Melanoma: radial growth in epidermis, superficial dermis Fig. 25-7, Robbins Pathologic Basis of Disease, Elsevier 2010

Malignant Melanoma: radial & vertical growth phases Radial growth: infiltration into epidermis & upper dermis Vertical growth: downward infiltration into dermis pleomorphic melanocytes in dermis

Blastocyst containing pluripotent Stem Cell Reminder Totipotent Stem Cell Blastocyst containing pluripotent Stem Cell

Teratoma It is a special type of mixed tumour. It originates from the totipotent germ cells such as those normally present in ovary & testis. These germ totipotent cells are sometimes abnormally present sequestered in midline embryonic rests (in head & neck, mediastinum, retroperitoneum & sacrococcygeal region). It is formed of tissues representative of more than one germ cell layer and sometimes the 3 (ectoderm, mesoderm & ectoderm). Thus capable of differentiating to any cell type present in adult body.

Teratoma Benign Mature Teratoma: is formed of mature well differentiated tissues. It can be monodermal consisting of one tissue only as thyroid (strauma ovarii) Immature Teratoma: consisting of immature (fetal type) tissues and behave in a malignant manner Mature Teratoma with a malignant transformation (Malignant Teratoma): transformation of one tissue in the mature tissue to malignant counterpart as squamous cell carcinoma in mature teratoma

Benign Mature Teratoma Figure 7-4 A, Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. You do not need a microscope to appreciate this tumor produces both connective tissue as well as epithelial derived elements. Remember, pure “epithelial” tumors may evoke a fibrous response, such as breast or pancreas or prostate adenocarcinomas, but the connective tissue us regarded as NON-neoplastic.

Immature Teratoma Low grade myxomatous stroma & primitive tubular structure Primitive neuro-epithelium

Blastomas (Embryomas) They are a group of mainly malignant tumours which arise from embryonal or poorly differentiated cells (primitive cells) which appear small round cells with darkly stained nuclei They occur more frequently in infants & children (under 5 years) e.g. neuroblastomas, nephroblastoma (Wilms tumour), hepatoblastoma, retinoblastoma, pulmonary blastoma & medulloblastoma.

Tumour like Conditions It was traditionally been considered a congenital malformation but recently it is suggested to be a neoplasm (benign tumour) formed of tissues normally present in this site but in a disorganized form e.g. lung hamartoma (islands of cartilage, bronchial epithelium, smooth muscles, & blood vessels) and liver hamartoma Hamartoma

Hamartoma: An example in the lung clefts lobulation Gross: Well circumscribed mass present at the periphery of lung, formed of: glistening lobulated nodule of cartilage having few clefts. Lobules of mature cartilage, clefts lined by respiratory-epithelium, fat, smooth muscle cells, and blood vessels.

Tumour like Conditions Choristoma (Heterotopia) A congenital anomaly forming a mass of non neoplastic normal tissue in a foreign location Examples: Pancreatic tissue in stomach, duodenum or small intestine Brain tissue in nasal cavity

Take Care Please identify the behaviour of the following tumours as whether benign or malignant? Misnomers Hepatoma: malignant tumor arising from hepatocytes Melanoma: malignant tumor arising from melanocytes Lymphoma: malignant tumor of lymphocytes Seminoma: malignant testicular tumor (seminiferous tubules) Pathology Department

Formed of Match Masses of basaloid cells showing peripheral palisading of the nuclei with no central keratin. Variably shaped and sized glands lined by columnar cells showing nuclear criteria of malignancy Masses and sheets of malignant epithelial cells having eosinophilic cytoplasm, large vesicular nuclei and prominent nucleoli with central keratin formation Lakes of mucin in which remnants of glands and signet ring cells are floating. 3 Adenocarcinoma Mucoid carcinoma Basal Cell carcinoma Squamous Cell Carcinoma Squamous cell papilloma Adenoma 1 4 2

Identify which of the following statements is true and which is false & CORRECT the false ones: Benign tumours are always well differentiated while malignant tumours are always poorly differentiated Hepatoma is a benign tumour of liver cells while melanoma is malignant tumour of melanocytes Hamartoma was thought to be a congenital anomaly but now it is considered to be of neoplastic origin Teratomas originating from the totipotent germ cells arise only in the ovary and testis F F T F Pathology Department