Microscopically Yours: A Glimpse at our Cells, in

Sickness and in HealthNina C. Zanetti

Siena College

Department of Biology

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• Is it cancer ??• If it is… how serious

is it?

• Will I need treatment? What kind?

Next step in the journey….

• “We need to look at the tissues. We need a biopsy.”– Is it cancer or is it

benign ?

– Is it invasive?

– What treatments?

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Histology will answer our questions !

• Histology: study of normal tissues

• Pathology: study of diseased tissues

• Tissue: – Building blocks of organs– group of cells working together to carry out a

specific function

• Biopsy: small bit of tissue removed from patient for examination with microscope

Tissue: •Building blocks of organs•Group of cells working together to carry out a specific function

From Biopsy to Pathology report

?

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From Biopsy to Pathology report

?1. Biopsy specimen microscope slide

(histotechnique)2. Interpretation of slide pathology report

(pathologist)

From biopsy specimen to microscope slide: HISTOTECHNIQUE

DIAGRAM: Kessel, Basic Medical Histology, Oxford University Press. Why thin section?

Why paraffin?

“why is it taking so long?”

Why “fix” and process ?

From biopsy specimen to microscope slide:

tissue fixation and processing

From biopsy specimen to microscope slide:

infiltrations and embedding

From biopsy specimen to microscope slide: sectioning

From biopsy specimen to microscope slide: staining

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From biopsy specimen to microscope slide:

The finished microscope slide

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Limitations of histotechnique

• Tissue is dead

• Only a slice: 2D

• Color artificial:– Purple nuclei– Pink cytoplasm

• Need to know “what is normal”

From microscopy slide to Pathology Report: POWER of Histotechnique

Specimen: Clinical History49 year old female who was found to have a mass (or calcifications) on physical exam (or mammography). Stereotactic core biopsy reveale malignancy. Clinical Diagnosis: Right breast cancer

Microscopic Description Slides A3- A4 consist of a portion of breast tissue in which is located an infiltrating ductal carcinoma of the breast. The malignancy is characterized by infiltrating nests of malignant cells in which there is only, focal tubule or glandular formation. The cells demonstrate a moderate degree of nuclear pleomorphism, with some of the cells having central nucleoli. However, the mitotic rate is less than 1 mitosis per 10 high power fields. Overall the carcinoma is grade II. Adjacent to the carcinoma are areas of ductal carcinona in situ. Histologically the tumor is 2mm from the inked margin. No lymphatic invasion is appreciated.

Diagnosis Infiltrating ductal carcinoma of the breast, Grade IIFoci of ductal carcinoma in situ Tumor is 2 mm from the inked margins Metastatic cancer in 2/12 lymph nodes.Markers The tumor is estrogen receptor positiveThe tumor is Her 2 neu positive

From Biopsy to Pathology report

?1. Biopsy specimen microscope slide

(histotechnique)2. Microscope slide Interpretation of

slide pathology report (pathologist)

From microscope slide to Pathology Report

?“Reading” the Slide

From microscope slide to Pathology Report:

Interpreting NORMAL Tissue

structure (Histology)

Four basic tissue types

• Epithelium

• Connective tissue

• Muscle tissue

• Nerve tissue

Four basic tissue types

• Epithelium : the “lining” tissue

• Connective tissue : connects and supports

• Muscle tissue: movement

• Nerve tissue : communication

Epithelial tissue

Characteristics of epithelial tissue:

• Where is it found?– Lining spaces, covering surfaces

• How are cells arranged?– Tightly packed, in layers

• Good at repair/regeneration?

• Polarity? Cells have different surfaces

• Functions? Protect, seal, secrete, absorb,

Connective tissue:

Characteristics of connective tissue:

• Where is it found?– Connecting tissues and organs

• Cells + fibers + jellies

• How are cells arranged?– Dispersed; fibers and jellies in between

• Variations?

Muscle tissue:

Characteristics of muscle tissue:

• Where is it found?– Where movement is needed.

• Cells: striped or dark pink “spindles”

• Variations?– Yes - both structural and functional!

• Functions?– Movement!

Nerve tissue:

neuron

Characteristics of nerve tissue:

• Where is it found? – Brain, spinal cord, other organs

• Special cells: neurons

• What do neurons look like?– Large cell, extensions, owl-eye nucleus

• Functions?– Communication!

Practice with normal histology: • Epithelium:

– Lining– cells in layers, tightly packed.

• Connective tissue– Cells + fibers+ jellies– Cells dispersed in matrix

• Muscle:– striped or spindles

• Nerve:– neurons with extensions and “owl eye” nuclei

Practice with normal histology: epithelium, connective tissue, muscle , or nerve? 1

Practice with normal histology: epithelium, connective tissue, muscle , or nerve? 2

Practice with normal histology: epithelium, connective tissue, muscle , or nerve?

3

Practice with normal histology: epithelium, connective tissue, muscle , or nerve? 4

From microscope slide to Pathology Report

?“Reading” the Slide

From microscope slide to Pathology Report:

Understanding Diseased Tissue structure (Pathology)

What can go wrong?

• Right cells in the wrong place

• Tissue injury: inflammation

• Good cells gone bad: cancer

Pathology: right cells in the wrong place (Barret’s Esophagus)

Pathology: right cells in the wrong place (Barret’s Esophagus)

Esophagus, normal epithelium

Small intestine, normal epithelium

Pathology: right cells in the wrong place (Barret’s Esophagus)

Esophagus, normal

Small intestine, normal

Biopsy specimen

Pathology: Tissue injury (inflammation)

Inflammation: the body’s response to injury

Cells of peripheral blood, human blood smear

lymphocyte monocyte

basophileosinophilneutrophil

Cells of the inflammatory response

lymphocyte

monocyte

neutrophil

Neutrophils in acute inflammation, stomach

Lymphocytes in chronic inflammation, appendix

Pathology: Good Cells Gone BadCANCER

• Won’t stop dividing (mitosis)

• Weird nuclei

• Don’t stay at home– Invade– metastasize

CANCER: Good Cells Gone BadWon’t stop dividing (mitosis)

Onion root tip cancer of uterus

CANCER: Good Cells Gone BadWeird nuclei

Normal epithelium bladder cancer

CANCER: Good Cells Gone BadDon’t stay at home

Normal epithelium Invasive breast cancer

Practice with pathology: which is normal (bladder), which is cancer?

Practice with pathology: which is normal (uterus), which is cancer?

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• Is it cancer ??• If it is… how serious

is it?

• Will I need treatment? What kind?

The journey…. Waiting for the Pathology Report

– Is it cancer or is it benign ?

– Is it invasive?

– What treatments?

http://www.breastcancerlaw.com/counseling.jpg

From Biopsy to Pathology report

?1. Biopsy specimen microscope slide

(histotechnique)2. Interpretation of slide pathology report

(pathologist)

Is it cancer?

Is it invasive?

What kinds of treatment? Are hormone receptors present?

The journey continues….

– Is it cancer or is it benign ?

– Is it invasive?

– Has it metastasized?

– What treatments?

http://www.breastcancerlaw.com/counseling.jpg

Microscopically Yours: A Glimpse at our Cells, in

Sickness and in Health