11. Neoplasia I_Lewin_NOTES.pdf

NEOPLASIA I Nomenclature and Characteristics David N. Lewin, M.D. [email protected] 843-876-5608 OUTLINE: 1. Definitions a. Neoplasia 2. Nomenclature a. Benign Tumors b. Malignant Tumors 3. Characteristics Of Benign And Malignant Neoplasms a. Rate Of Growth b. Differentiation And Anaplasia (Grade) c....

NEOPLASIA I Nomenclature and Characteristics David N. Lewin, M.D. [email protected] 843-876-5608 OUTLINE: 1. Definitions a. Neoplasia 2. Nomenclature a. Benign Tumors b. Malignant Tumors 3. Characteristics Of Benign And Malignant Neoplasms a. Rate Of Growth b. Differentiation And Anaplasia (Grade) c. Local Invasion (Stage) d. Metastasis (Stage) Objectives: After studying this unit you should be able to: 1. Understand the difference between neoplasia and hyperplasia 2. Develop a working knowledge of the nomenclature of benign and malignant neoplasms 3. Compare the clinical and morphologic characteristics which distinguish benign and malignant neoplasms 4. Understand the meaning of differentiation and anaplasia and how they relate to neoplasms 5. Know the three pathways of metastasis and the characteristic neoplasm that spread in that manner. READING REFERENCE: Pp 189-196, Robbins Basic Pathology, Tenth Edition page 175 David N. Lewin, M.D. Neoplasia I REVIEW QUESTIONS Select the best answer: ____ 1. A 45 year old woman has a chest x-ray taken and is found to have a peripheral "coin lesion" that is a rounded, circumscribed 2.5 cm mass in the right mid-lung field. She has no chest pain, cough, or fever. The biologic characteristic that best distinguishes this lesion as a neoplasm, rather than a granuloma, is: A. B. C. D. E. Necrosis Rapid increase in size Recurrence following excision Sensitivity to radiation or chemotherapy Uncontrolled (autonomous) growth ____ 2. A 35-year-old woman had a firm nodule palpable on the dome of the uterus six years ago on routine examination. The nodule has slowly increased in size and is now appears to be about twice the size it was when first discovered. She is asymptomatic. The uterine nodule is removed and examined microscopically, revealing benign smooth muscle cells. What is the most likely diagnosis? A. B. C. D. E. Adenocarcinoma Hematoma Leiomyoma Leiomyosarcoma Metastasis ____ 3. A healthy 22-year-old woman has a routine physical examination and a discreet, firm, rubbery, movable mass is found in the left breast. She has no axillary lymphadenopathy. The skin overlying the breast and the nipple appear normal. Which of the following neoplasms is most likely to be present? A. B. C. D. E. Fibroadenoma Intraductal carcinoma Leiomyoma Lipoma Malignant lymphoma page 176 David N. Lewin, M.D. Neoplasia I ____ 4. A 32 year old woman has had some dull pelvic pain for the last two months. An abdominal ultrasound reveals a mass involving the right ovary that is 8 cm in diameter. The mass is surgically excised. The surface of the mass is smooth, and it is not adherent to surrounding pelvic structures. Grossly, the mass is seen to be cystic and filled with hair on sectioning. Microscopically, there is squamous epithelium, tall columnar glandular epithelium, cartilage, and fibrous connective tissue. The most likely diagnosis is: A. B. C. D. E. Choristoma Hamartoma Mesothelioma Myxoma Teratoma ____ 5. A 62 year old man has complained of pain on urination. On cystoscopy, a slightly erythematous 1 cm diameter area is seen on the bladder wall. This area is biopsied and microscopically, the epithelium shows cells with marked hyperchromatism and increased nuclear/cytoplasmic ratio involving the full thickness. However, these changes are confined to the epithelium above the basement membrane. This process is best described as: A. B. C. D. E. Carcinoma in situ Hyperplasia Low grade dysplasia Metaplasia Microinvasion ____ 6. A lump is felt in her right breast by a 56 year old woman. Her physician palpates an irregular 3 cm mass that is not movable because it appears fixed to the overlying skin, which is retracted. A mastectomy is performed and the pathologist on sectioning the breast finds a 3 x 3.5 cm ovoid mass that does not have discrete borders, but appears to infiltrate into the surrounding fibrofatty breast stroma. The mass is firm, white, and has a fibrous consistency. Which of the following features is demonstrated by the gross appearance of this mass: A. B. C. D. E. Anaplasia Aplasia Desmoplasia Dysplasia Metaplasia _____7. A biopsy is performed on a patient with a mass lesion that proves to be a neoplasm. Of the following histopathologic findings, the one that best indicates that a neoplasm is malignant is: A. B. C. D. E. Atypia Increased nuclear/cytoplasmic ratio Invasion Necrosis Pleomorphism page 177 David N. Lewin, M.D. Neoplasia I ____ 8. A 60 year old man who has a 90 pack year history of cigarette smoking has had a chronic cough for years. He has recently begun to lose weight. He has a chest radiograph that reveals a right hilar mass. Sputum cytology shows atypical, hyperchromatic squamous cells. What is the most common initial pathway of spread of this lesion: A. B. C. D. E. Bloodstream Bronchi Contiguous spread to chest wall Lymphatics Pleural cavity Answers and explanations: 1. E: Objective #1 a. Uncontrolled growth is one of the characteristic features of neoplasia. While necrosis, recurrence following excision, rapid increase in size, and sensitivity to radiation or chemotherapy can all be seen with neoplasms, they also may be seen in infectious lesions. 2. C: Objective #2 a. The slow growth and benign smooth muscle cells identified microscopically make this a benign mesenchymal (smooth muscle tumor) = leiomyoma. Leiomyosarcoma is the malignant smooth muscle tumor. Hematoma is a blood clot (a non-neoplastic tumor or mass). Adenocarcinoma is a glandular malignancy. Metastasis are malignant tumors that have travelled from the organ of origin to another site. 3. A: Objective #2, 3 page 178 David N. Lewin, M.D. 4. 5. 6. 7. Neoplasia I a. A young individual with a round, rubbery movable mass in the breast is most likely a benign breast lesion. Fibroadenoma (a benign breast lesion made up of benign fibrous stroma and benign glandular tissue) is a very common benign tumor (mass) found in young women. Of the distracters, lipoma (benign tumor of fat) and leiomyoma (benign tumor of smooth muscle) are the two other benign lesions. Both can be found in the breast, although lipomas are less likely to be firm and leiomyomas are an unusual tumor of the breast (more common in the uterus). Intraductal carcinoma and lymphomas are malignancies and unlikely to have this presentation. E: Objective #2 a. The key for this question is the identification of multiple cell or tissue types from different germ cell layers (epidermal [squamous epithelium], mesodermal [cartilage and fibrous connective tissue], and endodermal [glandular tissue]). Teratomas are neoplasms arising from totipotential germ cells. Choristoma is an congenital anomaly with heterotopic rest of cells (benign cells in an abnormal location). In contrast, hamartoma is a benign mass of disorganized tissue indigenous to the particular site. Mesothelioma is a malignancy arising from the mesothelial cells lining the abdominal, pleural and pericardial cavities. These lesions should be on the surface of the peritoneal organs and are not typically cystic. Myxoma is a benign neoplasm that typically has an edematous (myxoid) gross appearance. A: Objective #1 a. The marked hyperchromasia and increased nuclear cytoplasmic ratio imply a neoplasm, however the fact it is still confined by a basement membrane means there is no invasion, thus an in-situ lesion. This is an epithelial lesion, thus carcinoma in-situ. Hyperplasia is a reactive increase in the number of cells. There should not be hyperchromasia of the nuclei, nor an increased n/c ratio in each cell. A metaplasia is a conversion of cell type (in the bladder from the normal transitional cell into a squamous cell or intestinal type cell). This is not a neoplastic transformation, however may be the first step in carcinogenesis. It is usually secondary to an inflammatory process. Microinvasion is present in an invasive carcinoma and implies that the tumor has invaded beyond the basement membrane. Dysplasia is a neoplastic transformation of cells. Carcinoma in-situ is dysplastic, however it is high grade dysplasia (with marked hyperchromasia and increased n/c ratio) rather than a low grade dysplasia. C: Objective #3, 4 a. The description is that of an invasive malignancy, typically an epithelial malignancy (or invasive adenocarcinoma of the breast). The firm fibrous infiltrative features of the tumor are secondary to a desmoplastic (a mesenchymal response of the body to the tumor cells). Anaplasia refers to microscopic loss of the structural and functional differentiation of tumor cells. Aplasia is the lack of formation of a structure or cell type. Dysplasia and metaplasia are discussed above. C: Objective #3 a. The two absolute features of malignancy are tissue invasion and metastasis. Atypia (abnormal cell), necrosis (cell death), pleomorphism (abnormal cell shape), and increased nuclear/ cytoplasmic ratio are all page 179 David N. Lewin, M.D. Neoplasia I features that are seen in malignant cells, however can be seen in reactive cells as well. 8. D: Objective #5 a. The description is that of a squamous cell carcinoma of the lung. Epithelial malignancies typically initially spread by lymphatics to lymph nodes (which is why distant metastasis is worse than lymph node metastasis). Mesenchymal malignancies (sarcomas) tend to spread via bloodstream (and not lymphatics). Lung cancers can and do spread via the bloodstream and into the pleural cavity however these are typically more advanced lesions. Contiguous spread to the chest wall can be seen, but is more common in peripheral (rather than hilar) lesions. page 180 9/7/2022 Neoplasia I: Nomenclature and Characteristics David Lewin, MD Pathology and Laboratory Medicine MUSC Overview   Definitions Nomenclature    Benign vs Malignant Epithelial vs Mesenchymal Characteristics of Neoplasms     Rate of Growth Differentiation and Anaplasia (Grade) Local Invasion (Stage) Metastasis (Stage) 1 9/7/2022 Definition- Neoplasia   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 evoke the change-Willis “New Growth”   Loss of responsiveness to normal growth control Neoplasm = Tumor Components of neoplasms:  Parenchyma (neoplastic cells)  Stroma (connective tissue and vessels) 2 9/7/2022 Tumor Fibrous tissue Fat Benign neoplasms (tumors)   Tumors which will remain localized, cannot spread to other body sites and which are amenable to surgical removal. Affected patients generally survive   Can occasionally have significant morbidity/ mortality Potential risk for malignant change 3 9/7/2022 Benign tumors- nomenclature   Named according to tissue type to which is added the suffix – oma. Examples:     Adenoma Lipoma Osteoma Papilloma 4 9/7/2022 Breast Fibroadenoma (Two parenchymal types) Abnormal N Fibrous mesenchymal elements Epithelial elements 5 9/7/2022 Benign Papilloma Benign papilloma (epithelial) 6 9/7/2022 Squamous Papilloma (benign wart) Hemangioma 7 9/7/2022 Hemangioma (notice all the blood) Leiomyoma 8 9/7/2022 Multiple Leiomyomas of the Uterus Pleomorphic Adenoma of Salivary Gland 9 9/7/2022 Pleomorphic Adenoma (Cartillagenous material and epithelial) Malignant tumors   Tumors which are capable of invasion (infiltration) and destruction of adjacent normal tissues. Most also have the capability to metastasize. Malignant = Cancer 10 9/7/2022 Malignant tumorsnomenclature  Named according to presumed histogenetic origin to which is added the suffixes:  Carcinoma- for malignancies of epithelial origin (differentiation)   Squamous cell carcinoma Adenocarcinoma Squamous cell carcinoma (epithelial) of the face 11 9/7/2022 Normal Squamous Epithelium Invasion into the stroma 12 9/7/2022 Breast Cancer Breast Carcinoma 13 9/7/2022 Breast Carcinoma Circumferential adenocarcinoma of the Colon 14 9/7/2022 Adenocarcinoma of the Rectum Malignant tumorsnomenclature  Sarcoma- for malignancies of mesenchymal origin (differentiation)   Osteosarcoma Chondrosarcoma 15 9/7/2022 Multiple benign leiomyoma Leiomyosarcoma Necrosis 16 9/7/2022 Liposarcoma Liposarcoma and adjacent kidney (normal) 17 9/7/2022 Additional Terms  Hamartoma: Mass of disorganized tissue indigenous to particular site  Benign, clonal, neoplastic   Traditionally considered developmental malformations Choristoma: Congenital anomaly of heterotopic nest of cells  Not neoplastic Rate of Growth  In General    Benign tumors grow more slowly than malignant ones Rate of growth correlates with level of differentiation (grade) Influences    Hormonal effects Blood supply Surrounding Tissue 18 9/7/2022 Differentiation and Anaplasia   Differentiation: Extent to which neoplasm resemble their parenchymal cells of origin: Morphologically and functionally Anaplasia: Lack of differentiation   Blastoma: Anaplastic tumor (often Pediatric) Informs grade of tumor (next lecture) Dysplasia   Disorderly proliferation Typically discussed with epithelial lesions   Precursor lesion to carcinoma Has many similar cellular features to those seen with carcinoma 19 9/7/2022 Morphologic predictors of malignancy- Cellular      Nuclear and cellular pleomorphism Nuclear hyperchromasia Nucleus/cytoplasmic ratio altered in favor of nucleus Abundant or abnormal mitoses Abnormal or absent cytoplasmic differentiation (anaplasia) Pap smear: Normal squamous cells 20 9/7/2022 Pap smear with Dysplasia Squamous cell carcinoma with marked nuclear pleomorphism and anaplasia. Abnormal mitotic figures. 21 9/7/2022 Morphologic predictors of malignancy- tissue     Lack of proper tissue organization (Dysplasia) Disordered maturation (Dysplasia) Infiltrative, destructive growth (Malignancy) Metastasis (Malignancy)    Seeding (Typically intraperitoneal) Lymphatics (Carcinomas) Hematogenous (Sarcomas) 22 9/7/2022 Infiltrative destructive growth of squamous cell carcinoma Peritoneal seeding (Ovarian tumor involving Omentum) 23 9/7/2022 Lymphatic infiltration by breast adenocarcinoma Colonic adenocarcinoma metastatic to liver (Hematogenous spread) 24 9/7/2022 Metastatic breast adenocarcinoma to the ovaries Comparison of Benign and Malignant Tumors 25 9/7/2022 Summary   Definitions Nomenclature    Benign vs Malignant Epithelial vs Mesenchymal Characteristics of Neoplasms     Rate of Growth Differentiation and Anaplasia Local Invasion Metastasis 26