Neoplasia (6 of 6)

This is the last lecture …so we will discuss:

• A low dose of “laboratory investigations in cancer”

• A low dose of information about germ cell tumors (just if you hear about)

• A note about stepwise carcinogenesis

• A low dose about amyloidosis (not of neoplasia topics)

… but you must be familiar with it generally in medicine

Laboratory investigations

• For routine morphologic techniques:

… sampling methods:

- excision or biopsy…for histopathologic examination

- fine-needle aspiration, and cytologic smears

… for cytopathologic examination

*Frozen section…a sample is quick-frozen and sectioned, permits

histologic evaluation within minutes…e.g., to assess

margins or sentinel lymph node status during surgery, and

this is important for the surgeon to take decision on the

patient while he is still in the operation room

Fine needle aspiration

•Especially for breast, thyroid, lymph nodes, and salivary glands palpable lesions…can be ultrasound-guided

…can also be used for deeper structures, such as pancreas (through

duodenoscopy)

Papanicolaou smears (Pap smear)

• Pap smear is a name of a stain (like H&E, Giemsa…etc.) that is used for cytopathologic examination (which means for fluid samples, smears and FNAs)

• It is good in showing nuclear features

• Historically, this approach has been used widely for discovery of carcinoma of the cervix and its precancerous lesions

… so it is common to call cervical smears: Pap

smears

Robbins basic pathology 9th edition

Immunohistochemistry

•Detection of antigens

•Examples:

…prostate adenocarcinoma is positive for PSA (prostate specific

antigen )

…colon adenocarcinoma is positive for CK20 (cytokeratin 20)

…thyroid carcinoma is positive for thyroglobulin

Flow cytometry

•Especially for typing of leukemias and lymphomas

…also depends on detection of antigens

…performed on fluids (mainly blood)

Tumor serum markers

• May be enzymes, hormones or other proteins secreted by the tumor

• Examples:

-PSA…prostate cancer

-CEA )carcinoembryonic antigens)…colon, pancreas…etc.

-Alpha fetoprotein…liver cancer

• Not enough for diagnosis but good in screening, assessment therapy, and detecting recurrence

Molecular pathology

• Remember these 3 titles for the future:

-In situ hybridization…FISH )fluorescent in situ hybridization) and others

… for genetic abnormalities

-Cytogenetics

… Karyotyping: like that which is used to diagnose Down syndrome…etc .

… can be used to detect chromosome abnormalities in cancer

-Polymerase chain reaction

… for genetic abnormalities

Germ cell tumors (Just if you hear about)

Germ cell tumors

• Typically occur in gonads (testis and ovary)

• May occur elsewhere where germ cells may be there as remnants from embryogenesis

• Examples :

-Seminoma…malignant, in testis

-Dysgerminoma…malignant, in ovary

-Teratoma (have components from the 3 lines of differentiation)…benign

-Immature teratoma…malignant

-Yolk sac tumor…malignant

-Embryonal carcinoma…malignant

-Choriocarcinoma…malignant

Multistep carcinogenesis

•As we discussed before, accumulation of genetic/epigenetic changes occur during cancer development

•The best example of this concept is the adenoma-adenocarcinoma sequence seen in colon

This is a sporadic example…but remember that also adenomas in FAP syndrome will accumulate mutations to become adenocarcinoma in a similar way

Colonic adenocarcinoma also occurs in a syndrome called: hereditary non-polyposis colon cancer (Lynch syndrome)…by a mechanism different from FAP …the mechanism in Lynch syndrome is abnormality in some DNA repair genes

Amyloidosis (Just if you hear about) …not a neoplasia topic

• Extracellular deposition of fibrillar proteins are responsible for tissue damage and functional compromise

…due to aggregation of misfolded proteins (which are soluble in their

normal folded configuration) or protein fragments

…different types of proteins according to the disease

… e.g., -AA protein in cases of chronic inflammations

- AL in case of multiple myeloma (malignant plasma cell neoplasm)

- A beta in case of Alzheimer

Amyloidosis, cont’d

Amyloidosis, cont’d

•The fibrillar deposits bind a wide variety of proteoglycans and glycosaminoglycans, including heparan sulfate and dermatan sulfate, and plasma proteins, notably serum amyloid P component (SAP)

•Special stain: Congo red stain…using polarized-light microscopy