Gen Path Lab 10-16-08 MHD Normal Pictures are from internets Pathology Pictures are from Robbins Other stuff was on MHD Website Jackie Kuziej

General Pathology Concepts, Case 1 Infarct Necrosis 70 year-old male with right costovertebral angle pain and hematuria, two days after being admitted to the hospital for acute MI. Costovertebral pain—back pain right under rib cage, (over the kidneys) Hematuria—blood in the urine What is the organ? Kidney, gross—see light colored (pale) parts, kind of wedge-shaped=think necrosis Also see a clot up above the necrotic area indicating ischemia Kidney, histology—see some blood (vascular congestion) around the light colored pale parts on virtual microscopy Don’t forget to identify glomerulus and neighboring tubule In area of infarct Glomerulus have lost nuclei---nuclei are ghosts You do see some nuclei—those cells are neutrophils (leukocytes) Been called b/c the cells are dying—the cytoplasm leak initiates the acute response Characteristic Structural Changes? Ghost like remnants of glomeruli and tubules—cell outlines remain but cell details are lost. Inflammatory process at interface of infarct and normal tissue Vessels dilated with RBC Pathologic Process? Ischemic or Infarct Necrosis Why? Due to embolism—mural (wall) thrombosis after MI. See “ghost-like” cells and inflammation

Renal infarction: gross specimen. The kidney is cut in half along its longitudinal axis, exposing the cortex (A) the medulla (B)) and a minor calyx (C). The pyramidal shaped infarct is pale as compared to the adjacent normal cortex. Why? The arrow points to a line of hyperemia that represents the interface between normal and necrotic tissue.

Thick arrow points to glomerulus in an area of coagulation (ischemic) necrosis. Thin arrow points to a glomerulus which is in the interface between necrotic and normal kidney.

Normal Kidney Glomerulus Note cells have nuclei!

Figure 1-19 Coagulative and liquefactive necrosis Figure 1-19 Coagulative and liquefactive necrosis. A, Kidney infarct exhibiting coagulative necrosis, with loss of nuclei and clumping of cytoplasm but with preservation of basic outlines of glomerular and tubular architecture. B, A focus of liquefactive necrosis in the kidney caused by fungal infection. The focus is filled with white cells and cellular debris, creating a renal abscess that obliterates the normal architecture. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

General Pathology Concepts, Case 2 Hemorrhagic Necrosis 70 year-old male complained of chest pain with inspiration. He developed hemoptysis and dyspnea. Pain w/inspiration? Infarct extends to the pleura, pleural irritation Inflammatory response Hemoptysis Coughing up the blood that is in his alveolus from the other circulation He has metastatic colon cancer and a swollen left leg. Swollen leg makes us think DVT to the lung Remember cancer patients are hypercoagulable Also immobility will cause clots to form

Case 2 On virtual histology you see lots of blood in the alveolar spaces Note you can tell arteries b/c they have more thick walls There are some pulmonary artery thrombi When you look on the walls of the thrombi you see strands, it is starting to set This is a Hemorrhagic Necrosis (infarct) Why? The lung has a dual blood supply One blood supply is infarcted, and the other blood supply bleeds into it What other organs have dual blood supply? Small intestine (celiac, mesenterics, arcades) liver

Lungs removed en-bloc during autopsy The arrow points to an embolus extending through the branches of a pulmonary artery.

Pulmonary Infarct (arrow)—WEDGE shaped Lung looks more “spongy” than the kidney It looks like there is a clot in this vessel. Remember the lung has dual blood supplies: pulmonary artery and bronchiole blood supply (from aorta) Pulmonary Infarct (arrow)—WEDGE shaped Pulmonary infarcts are typically pyramidal with base at the pleura Only about 10% of pulmonary emboli actually cause infarction. Why? In patients with adequate cardiovascular function, the bronchial arterial supply can often sustain the lung parenchyma despite obstruction of the pulmonary arterial system. .

Hemorrhage into infarcted lung alveoli Infarcted alveolar septa (note no nuclei—are “ghost like”)

Pulmonary arterial thrombus

Figure 4-17 Large “saddle” embolus derived from a lower extremity deep venous thrombosis and now impacted in a pulmonary artery branch. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

B, Sharply demarcated white infarct in the spleen. Figure 4-19 Examples of infarcts. A, Hemorrhagic, roughly wedge-shaped pulmonary infarct. B, Sharply demarcated white infarct in the spleen. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

Normal Lung Remember to look for areas that look more normal on pathology slides first!

General Pathology Concepts, Case 4 Acute Inflammation 15 year-old female with right lower quadrant abdominal pain and vomiting. Appendicitis, grossly See fibrinous exudate (do not write “pus” in patient charts) See normal pink on left hand side, then see dark purple area Appendicitis, virtual histology see neutrophils—look for their segmented nucleus They are filling the lumen along with the purulent exudate Cells with orange granules—eosinophils Mononuclear cells are probably lymphocytes Look at serosal surface (the outside)—see pink strands w/lymphocytes, that is the fibrinous exudate (white) that we saw grossly on the surface Look at mucosal surface—is partially necrotic

Mucosal necrosis Be sure to compare acutely inflamed appendix with normal appendix Inflammation throughout all layers of appendix

Normal Appendix

Serosal inflammation, predominantly neutrophils

For comparison, a normal appendix is shown above. Figure 17-66 Acute appendicitis. The inflamed appendix shown below is red, swollen, and covered with a fibrinous exudate. For comparison, a normal appendix is shown above. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

General Pathology Concepts, Case 5 Chronic Inflammation 90 year-old female with diverticulum of esophagus. Grossly w/esophagus, looks like “white snake”—see little puffy thing, is pink, is diverticulum Food retention, multiple episodes of infection Tags on body parts-A for autopsy; S for Surgical resection Note that inflammation of prolonged duration—active inflammation, tissue destruction, attempts at repair are proceeding simultaneously Presence of Mononuclear cells: Macrophage, Lymphocytes and Plasma Cells Healing will be by fibrosis

Esophageal mucosa Submucosal chronic inflammation—see ink-drop looking cells Which are lymphocytes (don’t see multi-segmented cells) Remember plasma cells have nucleus on side and “tail” of cytoplasm along it

Mononuclear inflammatory cells, predominantly lymphocytes THINK CHRONIC INFLAMMATION; Non-granulomatous (no granulomas w/frustrated TMMI)

Normal Esophagus w/clean submucosa

General Pathology Concepts, Case 6 Tuberculosis: Caseous Necrosis 54 year-old male with low-grade fever, cough and weight loss for 2 months Man has come from Mexico after living there for 18 months

Pulmonary Tuberculosis Ghon Complex—means that caseous necrosis is on the lung and in the lymph The cut surface of the lung reveals a subpleural granuloma (arrow). The subcarinal lymph nodes contain caseating necrosis (*).  

Caseating granuloma Central necrosis Normal looking alveoli

What’s a Granuloma? A granuloma is a nodule consisting mainly of epithelioid macrophages (special activated macrophages with abundant pink cytoplasm) and other inflammatory and immune cells as well as extracellular matrix. They are often surrounded by a lymphocyte cuff or fibrosis. Epithelioid-Activated-- Mphages can fuse together ---they are seen in chronic inflammation Granulomas form when the immune system fends off and isolates an antigen but is unable to completely destroy it. (Frustrated TMMI) The antigen is most often an infectious pathogen or a foreign body, but in many cases the offending antigen is not apparent (as in autoimmune disorders). Granulomas are seen in a variety of diseases, infectious and non-infectious. Infections that are characterized by the presence of granulomas include tuberculosis, leprosy, histoplasmosis, cryptococcosis, blastomycosis, coccidioidomycosis and syphilis. The major non-infectious granulomatous diseases are sarcoidosis, Crohn's disease, berylliosis, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary rheumatoid nodules and aspiration of food and other particulate material into the lung. An important feature of granulomas is whether they contain necrosis or not. A related term, "caseation" (literally: turning to cheese) refers to a form of necrosis that, to the unaided eye, appears cheese-like, and is typically (but not uniquely) a feature of the granulomas of tuberculosis.

(A) Center of granuloma showing caseating necrosis (amorphous debris). (B) Periphery of granuloma containing activated macrophages, lymphocytes and a giant cell (arrow).

necrosis Activated (epithelioid) macrophages

TB says “Hi! I’m in your macrophage causing problems!”

Figure 8-30 Primary pulmonary tuberculosis, Ghon complex. Ghon complex just means that the caseous necrosis is both in the lung and in the lymph node. The gray-white parenchymal focus is under the pleura in the lower part of the upper lobe. Hilar lymph nodes with caseation are seen on the left. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

General Pathology Concepts, Case 10: Metaplasia 45 year-old female with white plaques in the endocervix. She has had 5 children with no complications. Her previous pap smear showed inflammatory changes.

Virtual Histology Cervix should only have a simple columnar epithelium, glands come to surface in endocervix This cervix has a huge lining to it—metaplasia Stratified squamous instead Metaplasia just means one mature type of cell is replaced by another mature type Note that the lung goes from columnar to squamous when there is smoking Why does this happen? Infection, Adaptation to stress

Stratified squamous epithelium replaced the normal, simple columnar epithelium of the endocervix and endocervical glands. Note that the gland is partially lined by simple columnar epithelium (arrow).

Normal Cervix simple columnar epithelium

Normal on Left, Metaplasia on Right. Cervix.

Figure 1-7 Squamous dysplasia of the cervix, a precursor of squamous cell carcinoma. There is a lack of orientation of the squamous cells throughout the upper two thirds of the epithelium. Many of the nuclei are enlarged, are hyperchromatic, and have irregular nuclear margins. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

General Pathology Concepts, Case 11: Lipoma 40 year-old female with subcutaneous nodule in outer thigh. Was non-tender, soft, movable Nodule was excised, and the cut surface was yellow and lobulated Looks encapsulated, is well-circumscribed Encapsulated is usually benign

Why does it matter if nodule is movable or slowly growing? “If it is movable, it is removable” Those things generally mean benign neoplasm On virtual histology note the capsule on the edges The fat cells are not trying to penetrate the capsule Fat cells just look like spaces Well differentiated adipocytes with no evidence of atypia

Thin fibrous capsule adipocytes

General Pathology Concepts, Case 12 Malignant Neoplasm-Fibrosarcoma 44 year-old female presented with weight loss and lower back pain. On examination both her legs were swollen. CT scan revealed a large retroperitoneal mass encasing the inferior vena cava and right ureter.

What’s retroperitoneal? A useful mnemonic to aid recollection of the abdominal retroperitoneal viscera is SAD PUCKER: S = Suprarenal glands (aka the adrenal glands) A = Aorta/IVC D = Duodenum (except for its first portion) P = Pancreas (the head and neck of the pancreas (but not the tail) U = Ureters C = Colon (only the ascending and descending branches, but not the transverse or sigmoid ) K = Kidneys E = Esophagus R = Rectum Also- What’s Love Got to do, Got to do with it?

Mass encasing inferior vena cava and the right ureter? Inf vena cava—probably cause of swollen legs Right ureter—increased pressure to kidney (hydronephrosis) Retroperitoneal mass Malignant neoplasm, such as a fibrosarcoma, will infiltrate adjacent tissue, encasing or destroying organs. It is surrounding and encasing the IVC and RU. Neoplasm is interlacing bundles of malignant fibrocytes They are infiltrating the fat and are highly atypical (pleomorphic) See mitotic figures on virtual histology This is not good—you usually see mitotic figures in malignancy No capsule—it is infiltrating things—look at interface The cells do not look like normal cells, they are atypic

On low power, high cellularity is appreciated.

mitosis The neoplastic cells are highly atypical, pleomorphic and have large, hyperchromatic nuclei

General Pathology Basics, Case 13 Benign Fibroadenoma of Breast This 35 year-old female found a nodule in her left breast on self-examination. It was non-tender and firm but not attached to the skin or chest wall. On resection, it was found to be well-circumscribed , with a white, rubbery cut surface. Well-circumscribed and movable---generally benign—probably encapsulated Encapsulated tissue is compressed by the slowly expanding tumor When tumors are going to infiltrate or if they don’t have a capsule, they STICK DOWN

The neoplasm is well circumscribed, grey-white and multilobated. Fibroadenoma - Breast Description: The surgical specimen consists of a bisected fibroadenoma. The neoplasm is well circumscribed, grey-white and multilobated.

Adipose tissue “Capsule” and compressed breast tissue Stromal component Epithelial component

Stroma with well differentiated cells which lack atypia Epithelial cells, lack atypia (are uniform, do not vary in size or shape)

Figure 21-15 Fibroadenoma showing compressed, elongated ducts surrounded by neoplastic stromal tissue. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

Figure 23-1 Normal breast anatomy and anatomical location of common breast lesions. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

Figure 7-14 Fibroadenoma of the breast. The tan-colored, encapsulated small tumor is sharply demarcated from the whiter breast tissue. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

Figure 23-28 A, This mammogram shows a well-circumscribed mass Figure 23-28 A, This mammogram shows a well-circumscribed mass. Although the most common lesion would be a fibroadenoma, other benign (e.g., fibrous lesions or PASH) and malignant (e.g., medullary or mucinous carcinomas) lesions can also have this appearance. B, Fibroadenoma. A rubbery, white, well-circumscribed mass is clearly demarcated from the surrounding yellow adipose tissue. The fibroadenoma does not contain adipose tissue and therefore appears denser than the surrounding normal tissue on mammogram. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier

Basic Pathology Concepts Case 14: malignant epithelium neoplasm--Carcinoma This 58 year-old male smoker presented to the clinic with swelling and pain of the floor of the mouth. Ulcerated tumor involving floor of mouth and tongue: Neoplasm infiltrating oral structures—characteristics consistent with a malignant neoplasm Tumors have a tendency to ulcerate because it outgrows it’s blood supply and the middle part caves in. On examination he had an ulcerated tumor involving the floor of the mouth and tongue. Wide local excision was done.

The neoplasm infiltrates skeletal muscle. There is no capsule. Remember skeletal muscle cells have many nuclei that are pushed to the sides

They are the ONLY type of cell that does this. Malignancy. Also squamous cells form “intracellular bridges” which look like a ladder. They are the ONLY type of cell that does this. Malignancy. Large and small nests of squamous cells. Keratin pearl Malignant squamous cells trying to re-capitulate and mimic normal squamous mucosa by forming keratin pearl

Intracell bridges Mitosis Nests of atypical, pleomorphic squamous cells

Goljan Review Says… Leukoplakia literally means "white patch" (Fig. 17-3). Lesion does not wipe off. Erythroplakia is a red patch. Both lesions are due to squamous hyperplasia of the epidermis. Increased risk for squamous dysplasia or invasive squamous cancer Causes Chronic irritation (e.g., dentures) All forms of tobacco use, alcohol abuse, human papillomavirus (HPV) Locations Vermilion border lower lip (most common site) Buccal mucosa, hard and soft palates, floor of the mouth

Figure 17-3/Goljan: Leukoplakia of the tongue with invasive squamous cell carcinoma. Discrete raised white patches are evident on both sides of the tongue. Downloaded from: StudentConsult (on 16 October 2008 01:36 AM) © 2005 Elsevier