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

2. 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

3. 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

4. How can you describe these lesions?

5. 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.

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

7. 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?

8. Squamous Cell Carcinoma

9. 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

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

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

12. 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

13. 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

14. 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.

15. 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

16. 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.

17. 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 ….

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

19. 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

20. 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

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

22. 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

23. Mucinous Adenocarcinoma of Large Intestine
Signet ring cells
Extracellular mucin

24. Signet Ring Cell Carcinoma

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

26. 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

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

28. Malignant Mesenchymal Tumours (Sarcomas)

29. 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

30. 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

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

32. 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??

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

34. 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

35. 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

36. 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

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

38. Blastocyst containing pluripotent Stem Cell
Reminder
Totipotent Stem Cell
Blastocyst containing pluripotent Stem Cell

39. 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.

40. 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

41. 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.

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

43. 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.

44. 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

45. 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.

46. 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

47. 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

48. 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

49. 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