1. Vocabulary of Neoplasia
General Pathology C T. Davis

2. Metaplasia
METAPLASIA is a reversible change in which one adult cell type is replaced by another adult cell type. Note: the influence that predisposes to change, if persistent, may induce cancer transformation in the metaplastic epithelium. Examples:
Columnar-to-squamous (lung, cervix)
Squamous-to-columnar (esophagus)

3. Endocervix with squamous metaplasia

4. Normal esophagus

5. Barrett Syndrome

6. Barrett’s syndrome

7. Glandular metaplasia

8. Adenocarcinoma

9. Dysplasia
Term describing cells that have undergone proliferation and atypical cytologic alterations involving cell size, shape, and organization.
In models of neoplasia in many organs dysplasia is an antecedent of malignancy (both in-situ cancers and invasive tumors).

12. Moderate dysplasia
(dysplasia)

13. Carcinoma in-situ (CIS)
A preinvasive stage of epithelial malignancy which exhibits the cytologic features of malignancy but has not yet invaded beyond the confines of the native basement membrane.

14. Carcinoma In Situ of cervix (CIN III)

15. Carcinoma In Situ- mitoses throughout the epithelium

16. Early invasion by squamous cell carcinoma through the basement membrane

17. Pap Smears
Normal
Low Grade
Moderate
Severe/CIS

18. Definitions Neoplasia [G. neos, new + G. plasis, a molding]
- The pathologic process that results in the forrmation and growth of a neoplasm.
“Abnormal growth that continues”

19. Neoplasm [neo- + G. plasma, thing formed]
“A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.” Sir Rupert Willis

20. -OMA(S) [Greek suffix ‘-oma’ = tumor]
Examples of benign tumors: lipoma, fibroma, angioma, leiomyoma, rhabdomyoma, Schwannoma, neuroma, hepatoma

21. Adenoma [G. aden, gland + -oma]
A term applied to benign epithelial neoplasms that form glands, as well as to the tumors derived from glands but not necessarily reproducing glandular patterns.
Examples: cystadenoma, papillary cystadenoma, fibroadenoma

22. Malignant Neoplasms with “oma”
Carcinoma
Sarcoma
Lymphoma
Melanoma
Mesothelioma
Glioma

23. And: teratoma Tumor with components from 2 or 3 germ cell layers
Ovary- usually benign
Testis- usually malignant (in adults)

24. Ovarian Teratoma (“dermoid cyst”

25. Arrow indicates neural tissue; benign here, but sometimes malignant

26. Testicular teratoma

27. Tumors of Mesenchymal Origin
BENIGN
Fibroma
Lipoma
Osteoma
MALIGNANT (sarcomas)
Fibrosarcoma
Liposarcoma
Osteosarcoma (osteogenic sarcoma)

29. Tumors of Muscle Origin
BENIGN
Leiomyoma
Rhabdomyoma
MALIGNANT
Leiomyosarcoma
Rhabdomyosarcoma

30. Smooth muscle tumors of the myometrium

33. Benign smooth muscle of a leiomyoma

34. Tumors of Epithelial Origin (Carcinomas)
BENIGN
Squamous cell papilloma
Adenoma
Tubular adenoma (adenomatous polyp)
Fibroadenoma- breast
MALIGNANT
Squamous cell carcinoma
Adenocarcinoma
Colon carcinoma (adenocarcinoma)
Adenocarcinoma, (Ductal carcinoma)

35. Multiple adenomatous polyps

36. Adenocarcinoma of colon

37. Invasive adenocarcinoma of colon

38. Anaplasia Anaplasia = Lack of differentiation = undifferentiated
Anaplasia is considered a hallmark of malignant transformation.
Anaplastic features include:
- Cellular/nuclear pleomorphism
- Increased nuclear-cytoplasmic (N/C) ratio
- Nuclear hyperchromasia (increased DNA content)
- Large nucleoli

39. Anaplastic rhabdomyosarcoma

40. Generally, all benign tumors are well-differentiated
Malignant neoplasms, in contrast, range from well-differentiated to undifferentiated
Well, moderately well, and undifferentiated (poorly differentiated or anaplastic)
Grade 1, 2, or 3 (or I, II, III) with 3 the least differentiated)

41. Other Histologic Features of Malignant Neoplasms
Increased/atypical mitotic activity
Tumor giant cells
Abnormal architecture- sheets or masses of tumor cells growing in an anarchic, disorganized fashion with infiltration and destruction of normal tissues.

42. Anaplastic tumor with tripolar mitosis

43. Carcinoma
Malignant neoplasms of epithelial cell origin, derived from any of the three germ layers, are called carcinomas.
Examples of modifiers include: Squamous cell carcinoma, Adenocarcinoma, Renal cell carcinoma

44. Bronchogenic CA

45. Arrow indicates keratin “pearl”

46. SP SP
Squamous cell carcinoma with “squamous pearls” (SP)

47. * *
Intercellular bridges (*)

48. Pap Stain on sputum cytology: keratinized squamous cell carcinoma

49. Metastatic adenocarcinoma: immunohistochemistry + for thyroid

50. Sarcoma Cancers arising within mesenchymal tissue are called sarcomas.
Examples of modifiers include:
- leiomyosarcoma
- osteosarcoma
- fibrosarcoma

52. Osteogenic Sarcoma (osteosarcoma)

53. Differentiation
Differentiation refers to the extent to which parenchymal cells resemble comparable normal cells, both morphologically and functionally.

54. Differentiation and Tissue of Origin
A general rule is that neoplasms differentiate in the direction of their ‘parent’ tissue.
- Consider: Transitional cell carcinoma of the urinary bladder is more common than squamous cell carcinoma and adenocarcinoma in this site. Conversely, transitional cell carcinoma arising in the ovary and uterine cervix is quite unusual, though may occur.

55. Liposarcoma

57. Additional Concepts Rate of Growth
In general, the growth rate of tumors correlates with their level of diffferentiation, and thus most malignant tumors grow more rapidly than do benign lesions. High grade malignant tumors (Grade 3) are more aggressive
Local Invasion
Most benign tumors are well circumscribed, while cancers grow by progressive infiltration, invasion, and destruction of the surrounding tissue.

58. GRADING TUMORS Malignant tumors only
Degree of differentiation and mitotic rate
Grades I-IV (higher grades are more anaplastic)
Important for some tumors: breast, prostate, endometrium, astocytomas
Dysplasias of the cervix are “graded”
Grading is done by Pathologists

59. STAGING TUMORS How far has the tumor spread? Malignant tumors only
Based on tumor size (T), lymph node involvement (N), distant metastases (M)
Staging often involves: the Pathologist, radiology or other imaging, lab tests (tumor markers)
CIS is often referred to as Stage Zero

60. Pathways of Spread
Seeding of Body Cavities and Surfaces: carcinoma, mesothelioma, and thymoma
Lymphatic Spread: initial route of spread for carcinomas
Hematogenous Spread: utilized by sarcomas and carcinomas

61. Fibroadenoma of Breast
Benign; rubbery, well-demarcated
No invasion
No metastasis

62. Fibroadenoma

63. Benign ducts of a fibroadenoma

64. FIBROADENOMA
Benign ducts of fibroadenoma

65. Ductal Carcinoma
In Situ
DCIS

66. DCIS (Ductal Carcinoma In Situ)
Surgery Meds. Watch
Invasive (10 yrs.) % % %
Die Brest CA (10 yrs.) % 2% %

67. DCIS- “A Rose is Not a Rose”
400 “Healthy” Women Surveyed for choice of treatment if DIAGNOSIS IS “DCIS” but other term used
“non-invasive breast CA”- 53%: no surgery
“Breast lesion” %: no surgery
“Abnormal cells”- 69%: no surgery

68. Invasive

69. Invasive Ductal Carcinoma
Mammogram with carcinoma

70. Vascular invasion by invasive ductal carcinoma

71. BREAST CARCINOMA GRADING
Bloom and Richardson
Tubules present (1-3 points)
Nuclear atypia (1-3 points)
Mitoses (1-3 points)
Total score 3-5: Grade I (Well differentiated)
Total score 6,7: Grade II (Moderately differentiated)
Total score 8,9: Grade III (Poorly differentiated)

72. Well differentiated:
Tubules
Small nuclei
(Well Diff.)

73. Moderately differentiated:
Rare tubules/solid nests
Pleomorphic nuclei
(Mod. Diff.)

74. Poorly differentiated:
No tubules; pleomorphic
Many mitoses
(Poorly Diff.)

75. BREAST CARCINOMA STAGING
Stage 0 (in situ or CIS): 5-year 92%
Stage I. (<2 cm & LN-): 5-year 87%
Stage II. (2-5 cm & 0-3 LN+): 5-year 75%
*Stage III. (>5 cm & >4 LN+): 5-year 46%
Stage IV. Distant metastases: 5-year 13%

76. BREAST CARCINOMA OTHER
Estrogen receptor (+): tumor is stimulated by estrogen and can be treated with the “anti-estrogen” tamoxifen. This is palliation.
HER-2 Neu amplification: by immunostaining or FISH is seen in 20% of cases. If HER-2 Neu is amplified in the invasive tumor, the patient can be treated with Herceptin (Trastuzumab) or Tykerb (Lapatinib) . This is very expensive and tends to be used in high grade/high stage lesions that are HER-2 Neu positive.
Triple Negative Breast Carcinoma- negative for estrogen and progesterone recptors and no overexpression of HER-2-Neu (recently reviewed in NEJM 363: )

77. ER (+)

78. HER-2 Neu (+)

79. COLON CANCER Grading is not very helpful
STAGING: predicts clinical outcome (TNM)
No penetration of the muscularis mucosa (Tis); 100% cure rate
Penetration of muscularis propria (and maybe serosa too) but lymph nodes negative (T3); 70% cure rate
1-3 (+) lymph nodes (N1); 30% cure rate
Distant metastases (M1); rare cures

80. COLON CANCER
OTHER
50% of colorectal carcinomas show “ras” mutations; 50% of adenomas > 1cm also show ras mutations
CEA (carcinoembryonic Ag) can be used to follow patients after surgery
Deeply infiltrating tumors cause desmoplasia (fibrosis) and “apple core/ napkin-ring” appearance. Desmoplasia is also seen in breast carcinoma

81. Adenomatous polyps

82. Adenoma:
Crowded glands but
no atypia

84. Molecular model for colorectal adenocarcinoma

85. TNM Staging System

86. Colon adenocarcinoma

87. Metastases: Metastases
are tumor implants discontinuous with the
primary tumor.
*METASTASIS unequivocally
marks a tumor as malignant because benign
neoplasms do not metastasize.

88. Liver with metastatic carcinoma

89. Metastatic melanoma in liver and bone marrow

90. 2 additional Terms
Choristoma: An ectopic rest of ‘normal’ tissue. Normal tissue in an abnormal location. Examples include glial tissue in the tongue, breast tissue in the “milk line”, nodules of pancreas in the small bowel, and adrenal rests in the uterine broad ligament or spermatic cord.
Hamartoma: Mass of disorganized but mature specialized cells or tissue indigenous to the particular site. Hamartoma of lung is classically a mass of benign cartilage with or without, blood vessels, adipose tissue, etc. Hemangiomas are also called hamartomas.