PathoHisto Flashcards
invasive breast carcinoma
- Infiltrative growth- not well circumscribed.
- Desmoplasia.
- No myoepithelial cells seen in the tumorous glands= malignancy.
- The Nottingham histologic score is a scoring system to assess the grade, based on 3 different sub-scores (each given a grade from 1-3): structure (how many tumor cells form glands) + cytomorphology (nuclear atypia, polymorphism) + mitotic rate. Minimal grade:3, maximal: 9.
- Cytomorphology: 1. Carcinoma NST (Ductal): variable atypia. 2. Lobular: small, round tumor cells, usually slight/moderate polymorphism.
- Tumor cells form tubules, cribriform structures, nests and cords.
- In this slide- we can also see DCIS = Ductal carcinoma In Situ.
Basal cell carcinoma, KROMPECHER TUMOR - SKIN
Most common skin malignancy. Semi malignant = Invasive but no distant metastasis. Peripheral Palisading (parallel organisation of nuclei on nest’s periphery. May contain melanin, surface often ulcerated, artifact reaction due to shrinkage of cells. May cause local bone destruction.
Adrenocortical nodular hyperplasia
How can we see this is the Adrenal gland? It has an adipose capsule and cortex and medulla. The cortex is composed of Zona glomerulosa, Zona fasciculata, Zona reticularis, but here it is unorganized due to hyperplasia. Hyperplasia is typical for the prostate gland, and can also occur in uterus (pregnancy) and mammillary glands.
Kinds of Hyperplasia:
- Diffuse- thyroid gland.
- Nodular- parenchymal organs.
- Polyps- mucosal.
thyroid follicular adenoma - THYROID
Complete fibrous capsule, Most common benign tumour of thyroid. Follicular structures. Low colloid content. Benign cytomorphology : Slight atypia/polymorphism can occur, but it does not indicate malignancy. Cytological evaluation of the cells in the case of thyroid follicular neoplasm cannot indicate whether the tumor is malignant or bening.
Criteria of malignancy:
a) infiltration of the capsule
b) vascular invasion.
Non-Hodgkin lymphoma- extra nodal - stomach
Extra nodal disease refers to lymphomatous infiltration of anatomic sites other than the lymph nodes. Almost any organ can be affected by lymphoma, with the most common extra nodal sites of involvement being the stomach, spleen, Waldeyer ring, central nervous system, lung, bone, and skin.
This is a MALT lymphoma in the stomach, also DLBCL type. This tumor is related to H.Pylori infection. The stomach can be recognized via its normal gastric mucosa part, in the small part where it stayed intact. Most of the mucosal surface looks ulcerated. The tumor infiltrates all the way through the muscularis externa layer. Diffuse growth pattern in the stomach wall (DDG: diffuse type gastric cancer). The tumor cells show atypia characteristics (large, not cohesive, have large nucleoli) and look like blasts
Extracellular protein accumulation in the Liver- Amyloidosis
To confirm the presence of Amyloid, we use Congo red stain + Polarization microscope = apple green color.
- The eosinophilic extracellular substance that surrounds the more basophilic cells (hepatocytes) is the Amyloid.
- Amyloidosis is caused by long term inflammation, hematogenic disorder, cancer, etc.
fibroepithelial tumors - Skin
Both tumors here are benign, as the ducts are composed of 2 layers: intraluminal layer and an outer myoepithelial (clear cytoplasm) layer. If the myoepithelial layer disappears = malignancy.
• Fibroadenoma is the most common benign tumor of the breast (light pink). It is estrogen dependant, it has a fibrous troma + benign ductal epithelial proliferation.
Phyllodes tumor is rare (purple). It has a leaf like pattern, classified according to its mitotic rate, atypia of the stroma and stroma overgrowth. Hypercellular stroma with the same epithelium as in the fibroadenoma/
Thyroid papillary carcinoma
Most common form of thyroid cancer, most often occurs in young adults (women).
- Good prognosis.
- Lymphogenic metastasis (cervical LN) – can develop early on, but can be treated surgically.
- Infiltrative growth.
- Contains papillary and follicular architecture in variable proportions.
- Branching papillae, having a fibrovascular stalk.
- Desmoplasia.
- Characteristic cytomorphology: special nuclei:
a) Orphan Annie eye (=chromatin clearing)
b) Nuclear grooves (=coffee bean nuclei)
c) intranuclear cytoplasmic inclusions (ICI) Nuclei are overlaping, arranged with long axes in parallel alignment.
• Psammoma body (laminated concentrically micro calcification in the stroma) may be seen.
Liver Metastatic adenocarcinoma
Portal triads and hepatocytes can be seen. Fatty degeneration, Cholestasis (bile pigment in the cytoplasm). Basophilic area= tumor. It is well circumscribed = characteristic for metastases. Physiological liver does not contain glands. Zooming in the glands, we see malignant neoplastic cellular atypia = ADENOCARCINOMA. The primary tumor could be colorectal/ gastric/ breast/ lung for example.
Serous cyst adenofibroma - UTERUS
Most common ovarian tumour, benign tumour is composed of cysts and stroma. The normal epithelial lining of the fallopian tube is composed of 3 cell types: ciliated, secretory and Peg cells. Cysts covered by single layer of tall, columnar, ciliated cells resembling normal tubal epithelium
Endometrial typical hyperplasia
Thick endometrium (endometrium/myometrium ratio↑).
- Glands are dilated, cystic. The glands have pseudostratified epithelial lining, which mimics proliferative endometrium.
- Gland/stroma ratio is maintained- typical hyperplasia. (if it wasn’t maintained, and also the cells were atypical- then it would be called atypical).
- Endometrial hyperplasia occurs due to increased level of estrogen (obese) or low amount of progesterone (polycystic ovary disease)
Necrosis of palatine tonsils
How do we know it is a tonsil?
- Stratified squamous nonkeratinized epithelium
- Crypts, lymph nodules can be identified
- Lymphatic tissue - lymphocytes nucleus is basophilic, and has invisible cytoplasm.
Diagnosis: This is a coagulative necrosis. We can see a homogenous loss of organization; the outline of the cell is seen and the nucleus is absent.
active chronic gastritis
This is a specimen from a biopsy.
- There are no parietal or chief cells => this is the antrum of the stomach.
- Surface epithelium is ok, so no erosion or ulcer.
- In the lamina propria- many lymphocytes, plasma cells and eosinophils are seen. These are mainly cells of chronic inflammation. Also, neutrophils are seen which are the acute/active component of this inflammatory reaction.
- There is also an Intestinal metaplasia seen (goblet cells which are not usually found in the stomach). This happens due to the irritation.
- On macroscopy has Petechia hyperemic area, mostly the antrum is affected.
- Can be caused by over use of Aspirin or steroids.
- Counter measures: Proton pump inhibitors.
- Lack of vitamin b12 absorption due to lack of intrinsic factor.
- One of the agents that causes gastritis is helicobacter pylori causing chronic gastritis found on the surface of the mucosa, rod like bacteria. Can be seen with immunohistochemically reaction.
Invasive squamous cell carcinoma of the Cervix
The normal cervical epithelium is not present here. The basement membrane of the epithelium was destroyed and hence this tumor is invasive. The tumor is also seen inside lymphatic vessels. Desmoplasia can be seen (Tumor induced stromal reaction characterized by collagen rich connective tissue). Broad epithelium polymorphism. Cells are not round, have prominent nucleoli. The epithelium is anaplastic (is a condition of cells with poor cellular differentiaton, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells). This is a not well differentiated lesion (about grade 3)- aggressive tumor. Chronic inflammation infiltrate can be seen (lymphocytes).
Granulation tissue
Granulation tissue is a new connective tissue with microscopic blood vessels that are formed on the surface of a wound during healing process. Characterization of granulation tissue:
- Rich vascularization (angiogenesis, cuboidal endothelial cells).
- Edematous interstitium, with fibroblasts (the main cells in the tissue, which will produce the collagen for the creation of a scar tissue).
- Chronic inflammatory cell infiltrate (macrophages, lymphocytes), in recent granulation tissue granulocytes as well. Their role is to phagocytose old or damaged tissues and protect the healing tissue from another infection.
IRDS- infantile respiratory distress syndrome.
This is the lung of a pre-term baby. The alveoli are not completely open. This is an autopsy case. Hyaline membranes (protein rich exudate) are seen lining the alveoli. This is a new-born disease due to the lack of surfactant. Corticosteroids can be given to the mother to stimulate production of surfactant in the fetus.
Non-Hodgkin lymphoma- nodal DLBCL - Lymph Node
Non-Hodgkin lymphoma can be due to neoplastic proliferation of either B or T cell (less common). It can be classified according to the B-cell size. 1. Small B-cells: follicular/mantle/marginal according to the regions of the secondary lymphatic follicles. 2. Intermediate B-cells: Burkitt lymphoma, associated with EBV. 3. Large B-cells: diffuse large B cell lymphoma (DLBCL)- most common, and seen in this slide. DLBCL is a diffuse large B-cell proliferation, present in late adulthood (>50) as an enlarging lymph node or an extra nodal mass. Diffuse growth pattern can be seen – the basic structure of the lymph node disappears (no distinct follicles seen). Centroblast, immunoblast-like tumor cells (ratio of tumor cells >90%) can be seen, that are large with prominent nucleoli. Many mitotic figures à high proliferation.
Liquefactive necrosis of the brain
How do we know it is the brain? Fibrillar network with low cellularity (Neurons, axons, glial cells can be seen).
Diagnosis: This is a liquefactive necrosis. It is light eosinophilic and has irregular shape, we can see the loss of nuclei. The tissue is no longer compact, not homogenous, much paler. This is different from coagulative necrosis because we cannot see the cell outlines. This is a necrotic tissue that becomes liquified by enzymatic lysis of cells and proteins.
nodular melanoma - SKIN Main types of melanoma: • SSM (most common) =superficial spreading melanoma= epidermal + dermal components. • Lentigo maligna: in situ melanoma of sun exposed skin. • Nodular melanoma (worst prognosis) = only dermal component. • Acral lentiginosus melanoma
Malignant tumor of melanocytes. Distant metastases can occur anywhere, liver usually affected.
- Mostly arises de novo. Mostly arises in the skin, other sites of origin include oral and anogenital mucosal surfaces, esophagus, and can also be intraocular and conjunctival.
- Atypical cells, variable cytomorphology (epithelioid/spindle cells), atypical mitoses.
- Asymmetric tumor with ulceration.
- Tumor cells look similar in the superficial and deeper layers, they do not show signs of maturation.
- Solar elastosis in dermis- an accumulation of abnormal elastin, which occurs as a result of the cumulative effects of prolonged and excessive sun exposure, a process known as photoaging. •
alcoholic hepatitis
- Autopsy case.
- Fatty liver=yellowish liver parenchyma. In chronic cases may cause fibrosis or cirrhosis=grayish, firm liver parenchyma.
- Pattern of inflammation: Granulocytic infiltration between hepatocytes (not in portal spaces). Necrotic hepatocyte can be surrounded by granulocytes.
- Mallory-Denk body: hyaline deposits (eosinophilic) in hepatocyte’s cytoplasm (cytoskeletal degradation). These can be found as they are usually surrounded by neutrophils. These are not necessarily specific to alcoholic hepatitis.
- Fatty degeneration =fatty vacuoles in hepatocyte’s cytoplasm. • Congestion can also be seen here- sinusoids engorged with blood. • Centrilobular fibrosis (around central veins).
- Liver cell necrosis results fibrosis→ end stage=cirrhosis
Squamous cell carcinoma- larynx
We can see hyaline cartilage, seromucous glands, and stratified squamous non keratinized epithelium. The tumor is seen infiltrating= malignant. Can also be seen in lymph vessels. We can also see cellular atypia (cellular and nuclear polymorphism, larger and euchromatic nuclei, atypical mitotic figures). The tumor has areas that are well differentiated, and areas that are poorly differentiated. keratin pearls can be seen (keratin production of tumor cells because of their epithelial origin). Surrounding the tumor nest, we can see a vast connective tissue stroma= Desmoplasia. Etiology: smoking, alcohol intake (HPV detected in small % of cases).
signet cell carcinoma - Stomach
This is the body of the stomach. See the large gastric glands and parietal cells.
- There is no tumor mass. The tumor cells are very diffuse.
- The tumor cells are called signet ring cells and produce mucin (hence are positive for PAS staining).
- This tumor can be revealed by endoscopy. The tumor is not distinctively seen, but the thickness of the wall of the stomach can be measured. The thickening of the wall is called lintis plastica.
- This type of tumor occurs mainly stomach, but occasionally may occur in other GI organs, prostate, urinary bladder, breast.
- Usually advanced stage at the time of the diagnosis.
- Pas staining show signet ring cells all over the layer up to the serosa.
peptic ulcer
This is the body of the stomach. See the large gastric glands and chief cells.
- This is an ulcer and not an erosion as the lesion reaches the submucosa.
- Intestinal metaplasia can be seen (goblet cells which are not usually found in the stomach). This happens due to the irritation.
- Peptic ulcer layers (from top):
- Necrosis with granulocytes and fibrin- looks eosinophilic.
- Granulation tissue- looks pale because it is edematous. This is edematous because the newly formed vessels of the granulation tissue are leaky.
- Scar tissue- connective tissue rich in collagen. In this slide it is not really seen, because the healing is not advanced enough.
- An ulcer can be acute (mostly in the stomach) or chronic (mostly in the duodenum or gastric antrum). The causes of an acute ulcer are hyperacidity, shock, stress. The causes of a chronic one are H.pylori, NSAID, smoking or alcohol.
- The consequences of an ulcer can be: Hemorrhage, perforation, scar formation.
foreign body granuloma- anorectal region
There is a transition between stratified squamous keratinized epithelium (typical to the skin) and simple columnar colonic mucosa. So, this is either a stoma (an artificial permanent opening especially in the abdominal wall made in surgical procedure) or the anorectal transition.
- This is a subtype of chronic inflammation.
- Giant cells can be seen inside granulomas, with foreign material embedded in them (from stitches of a previous operation).
- Macrophages are stimulated by IFN-gamma (secreted by Th1) to become epithelioid histiocytes and giant cells.
- This is a surgical specimen (we can see the black ink).
Metastasis of squamous cell carcinoma in lymph node
Encapsulated structure with secondary lymph follicles inside. Primary tumors can spread regionally, to form metastasis in nearby lymph nodes. For example: Bronchi tumor —>mediastinal lymph node. Uterine cervix tumor —> pelvic lymph node, Pharyngeal/laryngeal tumor —> neck region lymph nodes. Breast tumor —> axillary lymph nodes.
The metastases (pale area) are infiltrating the lymph node (darker, basophilic).
How can we know this tumor is of squamous cell origin? We can see keratin pearls, also no glands can be seen.
We can see the tumor as trabeculae surrounded by desmoplastic stroma.
Chronic myocardial infraction
There is high variability in myocytes’ caliber and nuclear size, because of the simultaneous degeneration, atrophy and regeneration in this tissue. We can see tissue scarring- highly fibrotic hypocellular area with fibrocytes and wavy eosinophilic collagen fibers.
MI => granulation tissue => scar.
The large scarring is because of macro-infracts, and the small diffused scars are due to micro-infracts (can only be seen by microscope). We can also see some healthy tissue remnants
Glioblastoma multiforme (GBM) - CNS/PNS
Gliomas are the most common group of primary brain tumors. these include astrocytomas oligodendrogliomas, and ependymomas. Infiltrative Gray Soft, hypercellular tumor. Differentiation: Grade I-IV. The presented slide contains glioblastoma multiforme (=grade IV). Solid tumor tissue, unorganized polymorphic cells (pseudopalisade arrangement around necrosis). Severe cytological atypia, frequent multinucleated giant cells. Necrosis & vascular proliferation
Arteriolosclerosis (hyaline type)- Kidney
Hyalinization- deposition of protein => Dysfunctional arteriole => Nephrosclerosis.
Hyaline arteriolosclerosis is a common pathological lesion of arterioles and results in a thickening of the vessel wall, and decreasing lumen size.
The deposition of hyaline material begins as a focal process that eventually involves the entire circumference of the vessel. The hyaline material is composed of precipitated plasma proteins, a major component being the inactive form of complement C3b.
This is a process of normal aging. Can be caused by DM (involves both afferent and efferent arterioles) and hypertension (only efferent).
Can lead to atrophy of the tubules and glomeruli, surrounded by chronic inflammation => chronic renal failure.
hepatocellular carcinoma (HCC)
Macroscopy: Solitary, rarely multifocal. Generally, well circumscribed nodules.
- Hepatocellular carcinoma is the most common tumor of the liver.
- portal/hepatic vein invasion → hematogenous metastasization.
- The basophilic (highly cellular) mass forming lesion is the tumor.
It shows: expansive growth, high cellularity, no desmoplasia. Loss of the hexagon unit and the trabeculae structure.
- Hepatocyte-looking tumor cells: large nucleus/cytoplasmic ratio, prominent nucleoli, bile secretion can occur. Forms rossete like formations. There might be hyaline (eosinophilic) bodies in the cytoplasm.
- Common necrosis/hemorrhage.
- Cirrhosis associated. We usually see cirrhosis when the tumor is a primary tumor and not a metastasis.
acute myocardial infarction
You can see the hyperemic boarder (the infarct has a wavy shape) is very basophilic because of the large number of neutrophils going towards the infarct to infiltrate it.
It separates between the normal myocardium (broader part) and necrotic myocardium of the infarct (narrower part)- seen better at the bottom. You can see the difference between the normal myocytes and the ones inside the infarct which are necrotic (no nucleus, no striations, highly eosinophilic).
Contraction band necrosis can also be seen in the margins of the infarct- irreversibly damaged myocytes after reperfusion develop contraction band necrosis. These are intense eosinophilic bands of hypercontracted sarcomeres that are created by an influx of calcium across plasma membranes. Inside the blood vessels stasis and clots (fibrin + RBC) can be seen
HPV infection- condyloma (LSIL= low-grade squamous intraepithelial lesion)
This specimen is surgical. Cauliflower proliferation (papillary lesion with connective tissue core). Condyloma acuminatum most commonly in HPV 6, 11. Low-risk HPV associated benign tumor of squamous epithelium.
This is a benign papilloma, that can be recognized by: Parakeratosis (we can see nuclei in the stratum corneum) may occur in the epithelium, or even keratinization of single cells. Koilocytes can be seen. They have irregular nuclei (enlargement, hyperchromatic, multinuclear cells) and perinuclear halo.
Atherosclerotic plaque atheromatous- coronary artery
The plaque has an outer fibrous layer (basophilic), and an inner core of cholesterol crystals, macrophages, calcification. This heart is taken from an autopsy case of a patient who had MI and so the coagulative necrosis (no nucleus stained, hyper-eosinophilic cells, no striations) is seen.
Near the remaining lumen, some new vascularization can be seen. Here we can see a soft unstable plaque that is prone to rupture and can cause emboli.
chronic pancreatitis
This is a surgical case.
Chronic pancreatitis can mimic malignancy and this is why a surgery is usually done.
- May be caused by recurring inflammations with mild symptoms (alcoholic/ hereditary/ autoimmune/ obstructive).
- Loss of parenchyma (acinus atrophy). Islets of Langerhans remained. First the exocrine function of the pancreas is lost and only after the endocrine.
- Lymphocytic infiltration- chronic inflammation.
- Fibrosis can be seen. Perineural fibrosis causes a lot of pain.
- the ducts are dilated and filled with secretions due to backflow.
- In chronic pancreatitis, mucinous metaplasia can develop. Pancreatic intraepithelial neoplasia (PanIN) is a microscopic neoplastic lesion of the pancreas that can progress to invasive ductal adenocarcinoma
clear cell renal cell carcinoma - Kidney
Most common malignant renal neoplasm.
- Mainly solitary. Often shows cystic degeneration, hemorrhage.
- High cellularity and vascularization, no Desmoplasia.
- Expansive growth pattern.
- Nesty/acinar structures .
- Clear cytoplasm (=glycogen and lipid rich), variable nuclear atypia and nucleoli (which determines the Fuhrman’s grade) no nucleoli visible with low magnification- low grade.
- Metastasis: most commonly hematogenous dissemination, direct tumor invasion to renal vein and vena cava => lung, brain, bone, suprarenal gland, liver.
- Highly associated with paraneoplastic syndrome.
- The symptoms are usually not clear.
Most typical: costovertebral pain.
Leiomyosarcoma uteri - UTERUS
Endometrial normal glands and the myometrium can be seen. Malignant proliferation of smooth muscle from the myometrium, arising “de novo”. Highly basophilic. Old uterine tissue, post menopausal, atrophy can be seen. Glands are narrow and less numerous. Tumour is well circumscribed. Multinucleated giant tumorous cells can be seen. Expansive, infiltrative growth, apoptosis on edges.
Squamous cell carcinoma of the lung
The cancerous cells are large, with a lot of cytoplasm. Have prominent nucleoli.
- Primary tumor centrally located (next to the bronchi). This may occlude the lumen and lead to repeating pneumonia.
- Tumor cell nests are surrounded by desmoplastic stroma.
- Keratin pearls can be seen, typical to squamous cell carcinoma.
- This has better prognosis than small cell carcinoma, and may sometimes be surgically removed.
- Antracotic, large, lymph node can be seen, with no definite metastatic signs in it.
- Large area of eosinophilia= necrosis.
Ductal carcinoma in situ (DCIS) - Breast - BREAST Types according to morphology: comedo, cribriform, solid, papillary, flat., Types according to nuclear morphology: Low – Intermediate – High grade.
This is the breast of a post-menopausal woman, as we see increased fatty tissue and smaller amount of acini.
- Tumor cells are very similar to each other- might be misdiagnosed as benign.
- Microcalcification is characteristic (mammography can reveal it)- can help distinguish it.
- Macroscopically invisible or difficult to detect: the whole breast can be affected.
- It can be detectable by Comedo necrosis (area of necrotic cancer cells which builds up inside the tumor). Associated with high grade DCIS.
- Malignant cells proliferate within acini (in TDLUs) and in ducts.
- Myoepithelial cells and basal membrane present at the periphery of affected, distended acini and ducts.