Lab Skills Pathology of Neoplasia PDF

Lab Skills pathology of Neoplasia Dr Rabab Ahmed Ahmed Mohammed Department of Pathology [email protected] Unit I Problem 10 Breaking Boundaries  SLOs (Specific Learning Objectives) Define the terms hypertrophy, atrophy, hyperplasia...

Lab Skills pathology of Neoplasia Dr Rabab Ahmed Ahmed Mohammed Department of Pathology [email protected] Unit I Problem 10 Breaking Boundaries  SLOs (Specific Learning Objectives) Define the terms hypertrophy, atrophy, hyperplasia, metaplasia, Dysplasia and neoplasia Correlate the nomenclature of benign and malignant neoplasia with their tissue of origin Distinguish between benign and malignant neoplasia Explain the methods of grading and staging of malignant neoplasms  Neoplasia Where all that come from? Tumors Come from abnormal cell growth Normal skin Skin cancer Normal cell growth = cell cycle  Disorders of cell growth Non Neoplastic Neoplastic (tumors) Hypertrophy Benign Atrophy Malignant Hyperplasia Metaplasia Dysplasia Reversible Nonreversible  Hypertrophy and atrophy Hypertrophy: Increase size of Atrophy: Atrophy is reduced the tissue due to increase size of the cells. size of an organ or tissue resulting from a decrease in cell E.g. Left ventricle hypertrophy (LVH) in patients with size and number hypertension This is cardiac hypertrophy involving the left ventricle. The number of myocardial fibers does not increase, but their size can increase in response to an increased workload, leading to the marked thickening of the left ventricle in this patient with systemic hypertension.  Microscopic appearance of Normal tissue (which means Normal cell growth) Architecture: All cells have same size and shape =uniformity of cells e.g surface epithelium- glands- Nucleus at bundles…etc the lower pole of the cell Cells: 1. Uniformity of cells 2. Preserved polarity Nucleus: Normal columnar epithelium stained with H&E mitosis Architecture: 1- Uniform (monomorphic) Glands/Ducts/tubules 2- Regular outline Normal stratified squamous 3- Mitosis: (few and normal and only in eрithelium; it has basal layer, the basal layer in case of stratified then layers of рolygonal cells squamous epithelium then superficial flat cells (this is called normal architecture / 4- Normal N/C ratio arrangement. All cells are uniform in size and shaрe N/C= Nucleus/cytoplasm ratio mitosis only in the basal layer Hyperplasia and metaplasia Hyperplasia : Increase number Metaplasia : Change of adult of cells due to increased cell type to another adult cell proliferation. May be type. physiological or pathological. It Adult cell=mature cell=differentiated cell is reversible Metaplasia is a reversible change in which one cell type (epithelial or mesenchymal) is replaced by another cell type  Dysplasia Zoom out Dysplasia: Disorderly but non-neoplastic proliferation of cells i.e loss of uniformity of individual cells and loss of their architectural orientation Architecture: 1. Disorderly arrangement of cells in the epithelium , Loss of maturation Cells: 1. Pleomorphic (variation in size and shape) 2. Lost polarity Nucleus: 1. Variation in size and shape 2. Nuclear enlargement and irregularity and Hyperchromatic nuclei Normal Dysplasia 3. Increased N/C ratio 4. Mitosis not confined to basal layer.  Dysplastic cells Normal cells Arrangement of cells Disordered arranged Cell size and shape Variation in cell size and Uniform shape (pleomorphism) Maturation Loss Normal preserved Polarity Loss Normal preserved Nuclear size & shape enlargement and Small uniform irregularity Nucleus Chromatin Hyperchromatic nuclei Normochromatic N/C ratio Increased N/C ratio Normal N/C ratio Mitosis Not confined to basal layer confined to basal layer  Dysplasia, how it progress? (evolution) Reversible: low-grade do not involve full thickness of epithelium. It may regress if persistent injury (smoking, HPV) is removed Progressive: high grade dysplasia affects most or full Normal Low High grade Carcinoma thickness of the epithelium grade dysplasia Insitu Invasive It may develop into carcinoma in-situ. dysplasia Carcinoma This happen (with persistent injury) →continuous proliferation of dysplastic cells.  What is a neoplasm Neoplasia literally means "new growth.“ Neoplasm can also be defined as a Benign Purposeless, autonomous cell growth. Tumor Malignant Tumor Benign vs. Malignant Neoplasm  Benign Malignant Growth rate slow growing Rapid growing Edges and Regular edges Gross Margins Well-defined Irregular edges margins poorly defined margins Pathological Invasion to No invasion Invasive features of surrounding Ts Tumors Localization Remain localized Invasive locally and though vessels Spreading Do not spread to Spread to distant sites distant sites  Classification and Nomenclature of benign and malignant neoplasia Neoplasms are named on basis of cell/tissue of origin. Main body tissue are: Epithelial Connective tissue (mesenchymal) Lymphoid/haematological Mixture of all (teratomas) Main classification and nomenclature of of Benign Trs Add suffix…..oma Squamous cell papilloma to the name of Surface Papilloma Transitional cell papilloma tissue Basal cell papilloma Epith. gland Adenoma Benign C.T Fat(Lipid) Lipoma Fibrous Fibroma Cartilage Chondroma Bone Osteoma Rhabdomyoma Muscle Leiomyoma  Main classification of Malignant Trs Epith. Surface …..carcinoma Squamous cell carcinoma carcinoma Transitional cell carcinoma Primary Basal cell carcinoma Add suffix…. gland Adenocarcinoma Carcinoma Sarcoma C.T Fat(Lipid) Liposarcoma to the name of Sarcoma tissue Fibrous Fibrosarcoma Cartilage Chondrosarcoma Muscle Bone Osteosarcoma Leiomyosarcoma Secondary Others Rhabdomyosarcoma Lymphoma  Other tumors: Lymphoma is a malignant tumor of lymphoid tissue (malignant) Cell of origin Benign Malignant Lymphoid ----- Lymphoma Haemopoieotic ------ Leukemia Melanocytes Neavus Melanoma Embryonic tissue Totipotential cells Teratoma Malignant teratoma Unipotential cells Retinoblastoma Neuroblastoma Nephroblastoma hepatoblastoma Melanoma Neavus (malignant) (Benign)  2 Teratoma of the 1 2 Ovary B ▪ Benign tumor ▪ Composed of mixture of mature tissues 1 (skin, hair, bone, A cartilage,….) C ▪ Other common site is the Teratoma: Tumors arising from germ cells composed of > 1 type of tissue which are not usually seen in that organ (A &B) Opened ovarian cystic testis but the testicular teratoma (1= solid nodule, 2= hair). (C) Section from nodule (S= skin and teratoma is malignant appendages, M= mucus glands, C= cartilage, R= respiratory epithelium)  Pathological changes in tumors and How to describe Gross Microscopic (Macroscopic) What is abnormal here? Can you describe the gross features of this abnormal growth Lesion: Number:? Edges:? Color:? Surrounding structure:? What is you diagnosis: It is a watermelon  How to describe Gross pathological changes Shape of the lesion: Ulcer, Nodule, Mass Polyp/ polyp,…etc Number of lesion: single, multiple, 2, 3 ,..etc Cauliflower Location: where? mass Shape: rounded, oval,…etc Size: Color: Nodule/ Surface: intact, smooth, ulcerated..etc Outline/Border: regular/irregular, well Mass demarcated/poorly demarcated…etc Relation to surrounding structure : invade into OR No invasion Ulcer  A Pathological lesion of the Uterus Normal Can you describe this Uterus tumor? Lesion: Number: Location: Shape: Size: Color: Outline/Border: Relation to surrounding structure:  A Pathological lesion of the Uterus Normal Can you describe this tumor? Uterus Well circumscribed masses Lesion: Nodule/masses Number: multiple (3 nodules) Location: wall of the uterus Shape: rounded Size: ~1 -1.5 cm Color: white Outline/Border: regular well demarcated Relation to surrounding structure: push with no invasion A Pathological lesion of the Uterus Normal Uterus Is it Benign or Malignant ? Benign Leiomyoma of the uterus Can you describe this tumor? Lesion: Polyp Number: Single Location: Above mucosa Mucosa Shape: rounded mass with a neck Size: ~2 x 2 cm Muscle layer Color: Brown Reddish Outline/Border: regular well demarcated Relation to surrounding structure: above surface with no invasion Cut section in the large colon Is it Benign or Malignant ? Benign Mucosa Muscle layer Adenoma of the Colon Cut section in the large colon  How to describe Parenchyma Microscopic pathological changes of tumors (A) parenchyma: Architecture/Arrangement :Tubules, : glands, sheets, cords papillae..etc Cellular features: 1. Size and shape of cells : Uniform or Pleomorphic is Stroma size and shape 2. Nuclei: Shape: Uniform or Pleomorphic is size and shape? Chromatin: Normochromic or Hyperchromatic? N/C ratio: Normal or Increased? mitosis: rare- frequent- normal or abnormal? (B)Stroma : connective tissue, blood vessels, host- derived inflammatory cells Benign malignant Sheets Tubules Cords Papillae Glands Different types of Architecture/Arrangement of tumor parenchyma  Benign Malignant Invasiveness NO invasion Invade surrounding tissue Cells shape, size Uniform Pleomorphic Nuclei Uniform in size Pleomorphic. and shape Benign Large irregular outline Mitotic figures Normal Abnormal Microscopic N/C ratio Normal High Chromatin Normochromic Hyperchromatic Necrosis Absent usually occur Pathological Differentiation Resemble tissue of has 4 grades of differentiation features of origin i.e. Well from well , moderate , poorly differentiated to anaplastic differentiated Tumors (i.e. not differentiated at all)  Benign Malignant Invasiveness NO invasion Invade surrounding tissue Cells shape, size Uniform Pleomorphic Nuclei Uniform in size Pleomorphic. and shape Benign Large irregular outline Mitotic figures Normal Abnormal Microscopic N/C ratio Normal High Chromatin Normochromic Hyperchromatic Necrosis Absent usually occur Pathological Differentiation Resemble tissue of has 4 grades of differentiation features of origin i.e. Well from well , moderate , poorly differentiated to anaplastic differentiated Tumors (i.e. not differentiated at all)  Differentiation Differentiation is defined by : How much the tumor resemble its tissue of origin. Differentiated tumors resemble their tissue of origin Benign tumors are well differentiated Malignant tumors has 4 grades of differentiation : 1. Well differentiated Fat cells 2. Moderately differentiated 3. Poorly differentiation 4. Undifferentiated (Anaplastic tumors)  Benign neoplasms ❑ Adenoma of the colon ❑ Leiomyoma of the Uterus ❑ Lipoma ❑ Teratoma of the ovary Adenoma ( colonic adenoma ) Polyp is a lesion / mass projecting into surface / lumen composed of epithelium surrounding a core and attached to tissue of origin with a stalk. (A) Resected colonic adenoma(adenomatous) polyp (B) Microscopic features of a adenoma , it is composed of glands (tubules) confined to the epithelial surface and core. The peripheral mucosa in (A) and (B) is normal colonic (glandular) epithelium A Adenoma B A Mucosa Normal Mucosa Normal  Leiomyoma of uterus The tumour composed of Composed of Spidle shaped smooth muscle fibres. Multiple masses Well differentiated. Location: within the Cells: are uniform in size and wall of the uterus shape Size: variable from 1-3 Normal N/C ratio cm Shape: rounded and Mitosis: rare and normal oval color: yellowish white edges: well demarcated and regular surrounding structure: push surrounding structure without invasion Leiomyoma of uterus Excellent prognosis - very rare to turn into malignant tumour Can you think in symptoms of the patient? Microscopically formed of bundles of smooth muscle fibres Lipoma Lipoma Lipoma Lipoma (MICROSCOPIC) (small intestine) (under the Skin) Nuclei placed on cell membrane Normal adipose tissue Malignant neoplasms ❑ Squamous cell carcinoma , lip ❑ Transitional cell carcinoma (kidney) ❑ Adenocarcinoma ❑ Endometrial carcinoma ❑ Breast carcinoma ❑ Metastatic carcinoma in the liver Squamous cell carcinoma , lip Describe the Gross features of the tumor? Edge: Raised everted Malignant Ulcer Outline: Irregular Edge: Raised everted Floor: red necrotic This is a cut section in the Ulcer  Well- differentiated squamous cell Malignant sheet carcinoma Keratin pearl Can you describe Malignant cells microscopic features?  microscopic features of (A) parenchyma: Well-differentiated Arrangement : irregular sheets of malignant cells squamous cell carcinoma invade below Basement membrane. These sheets have outer basal layer and keratin pearl in the center (these sheets are called cell nest) Cellular features: 1. Size and shape of cells : Pleomorphic is size and shape. Have pink cytoplasm and keratin pearl formation (nests) 2. Nuclei: Shape: Pleomorphic is size and shape Chromatin: Hyperchromatic Are all squamous cell carcinoma N/C ratio: Increased mitosis: frequent and abnormal well differentiated ? (B)Stroma : connective tissue, blood vessels, host- derived inflammatory cells No There are 4 grades of differentiation  Grades of Squamous cell carcinoma Malignant tumors are graded mainly according degree of resemblance to tissue of origin Well-differentiated Moderately –differentiated A squamous cell carcinoma B squamous cell carcinoma 1. Well-differentiated 2. Moderately differentiated 3. Poorly differentiated 4. Undifferentiated (Anaplastic) poorly -differentiated C squamous cell carcinoma D Undifferentiated squamous cell carcinoma Grading of squamous cell carcinoma (A) G1- Well-differentiated [most of the tumor has cell nests and keratin pearls] (Low grade, least aggressive) (B) G2- Moderately differentiated (Intermediate grade and aggressiveness). (C) G3- Poorly differentiated (D) G4- Undifferentiated (Anaplastic). (C) and (D) are high grade and rapidly aggressive.  Pathology Report Patient name:……………. Case #:……………………….. DOB:…………………………….Age:…………………………..Sex:…………….. Date specimen collected:………………………….. Date specimen received:…………………………………… Referred from Doctor:…………………………..Department:………….. History : ulcer at the right angle of the mouth for 6 months Type of biopsy: …………………………………….. Gross pathological examination: Discoid piece of skin and subcutaneous tissue measuring 1.5 x1.2 x 0.4 cm in size, showing irregular ulcer with raised everted edges. Microscopic examination: Well differentiated invasive squamous cell carcinoma with abundant keratin formation. The lesion is not completely excised. Transitional cell carcinoma, Kidney Transitional Cell Carcinoma of the Kidney Specimen: half of a kidney Description: The renal pelvis, is occupied by a papillary tumor mass. The tumor is friable and necrotic with areas of hemorrhage Microscopically : transitional cell carcinoma Test your knowledge 1. Q: what are the gross features of malignancy in this specimen? Answer:………….. Transitional epithelium 2. Q: What are other sites that this Lines the renal pelvis, ureters and tumor can originate from? urinary bladder Adenocarcinoma , Colon Lesion: ulcerative mass Describe the Gross Outline: Irregular Microscopic features of the tumor? Edge: Raised everted examination Floor: red necrotic  Can you describe microscopic features? (A) parenchyma: Arrangement : Malignant glands invade below Basement membrane Cellular features: 1. Size and shape of cells : Pleomorphic is size and shape 2. Nuclei: Shape: Pleomorphic is size and shape Chromatin: Hyperchromatic N/C ratio: Increased mitosis: frequent and abnormal Normal (B)Stroma : connective tissue, blood vessels, host- derived inflammatory cells colon mucosa  Grades of Adenocarcinoma Well-differentiated Moderately –differentiated A Adenocarcinoma B Adenocarcinoma Undifferentiated malignant tumors are called C poorly -differentiated Adenocarcinoma D Undifferentiated Adenocarcinoma Anaplastic tumors (they have the worst Grading of adenocarcinoma (A) G1- Well-differentiated (Low grade, least prognosis) aggressive). (B) G2- Moderately differentiated (Intermediate grade and aggressiveness). (C) G3- Poorly differentiated (D) G4- Undifferentiated. (C) and (D) are high grade and rapidly aggressive.  Abnormal mitosis is a feature of malignancy 11/7/2024  Endometrial carcinoma, Uterus (B) Malignant tumour involving the entire cavity 1 1 with 1=superficial myometrial invasion. 2 D 2=Incidental leiomyoma noted (D) Well differentiated 2 (grade 1) adenocarcinoma B (1) Cross section of normal uterus and (2) Normal endometrium  Breast A B carcinoma Describe the gross features Describe the C D Microscopic Breast cancer. (A,B, C) Cross sections of breast shows large irregular non- encapsulated invasive cancer associated with fibrosis as shown by retraction of features surrounding stroma and skin (D) infiltrating duct carcinoma  Spread (metastasis) OF malignant TUMOURS Metastasis It is the Process by which neoplastic cells from primary tumour spread to distant sites. Steps: 1. Primary tumour invasion into surrounding tissues, specially vessels (lymphatic or blood) 2. Then detachment within vessels and transport as emboli 3. Extravasation (move from vessel to tissue) and growth at distant sites Routs of distant spread: 3- Transcoelomic..i.e across body cavities e.g spread of malignant cells from gastric carcinoma too the ovaries 1- Blood vessels….leads to haematogenous through peritoneal cavity metastasis (liver, lung, bone and brain) Ovarian tumor Liver metastasis Ovarian tumor uterus Lung metastasis Ovarian metastasis Bilateral 2- Lymphatics Ovarian Cancer/ krukenberg tumor leads to lymph node involvement Lymph Node metastasis Metastatic malignant tumors in the liver Liver containing two large and many smaller metastases. Note the central necrosis within metastases. Necrosis within the nodules Thank you references: Robbins Basic Pathology, 11th edition, 2023