VMED 02610: Pathobiology I General Pathology – Neoplasia Lecture 3

What are the causes of direct effects

Caused by the physical presence of the tumor itself, at its primary or metastatic site

In direct effects: Tumors compromise organ function by

replacing (effacing) normal tissue and disrupting normal function

Under direct effects: Expanding tissue may compress

surrounding normal tissue or the blood vessels supplying it, resulting in pressure atrophy or necrosis

What is paraneoplastic effects

Indirect and usually remote clinically effects caused by substances the tumor cells produce and release

When can paraneoplastic effects occur

Can occur even when the tumor is small, distant, or not yet clinically detectable

What are the four major categories of paraneoplastic effects

 Cachexia

 Endocrinopathy

 Skeletal syndrome

 Vascular/hematologic syndrome

What does Cachexia look like and what does it mean

• Notable weight loss (muscle and fat) and debility

• Extra calories to not prevent or reverse cancer cachexia

Etiology is complex and multifactorial: WHY

 Cytokines and hormones that cause anorexia and debilitation

 Impaired digestion

 Nutritional demands of tumor tissue

 Nutrient loss in cancer-related effusions or exudates

 Metabolic and endocrine derangements

Cachexia can occur with almost every What

tumor type

What are endocrinopathies: endocrine tumors function

Functioning endocrine tumor produces the hormonal products of the tissue of origin, but without normal regulatory control

What is occurring in the endocrinopathies: Endocrine tumors

Increased numbers of hormone-secreting neoplastic cells, increased production of hormone by individual neoplastic cells, or both

What are encocrinopathies: nonendocrine tumors

• Nonendocrine neoplasm produces hormonally active substances not normally found in the tissue of origin

What are example for endocrinopathies: nonendocrine tumors

• Apocring gland anal sac adenocarcinoma (AGASACA)

• Lymphoma

• Multiple myeloma

all of hese then create parathyround hormone related peptides and then converts to hypercalcemia of malignancy

What is skeletal syndrome: Hypertrophic osteopathy

• extensive periosteal new bone growth, particularly on the extremities

• Associated with space-occupying thoracic lesions

What is the skeletal syndrome: Myelofibrosis

• overgrowth of nonneoplastic fibroblasts in the bone marrow

• Associated with local myeloproliferative diseases (lymphomas) or distant tumors

What is the vascular and hematological syndrome

• range of blood an coagulation abnormalities

Neutrophilia and eosinophilia cause what

alterations in circulating cytokine concentrations

Anemia causes what

anemia of chronic disease, bone marrow invasion, myelofibrosis, blood loss, and hemolysis

Thrombocytopenia causes what

hemangiosarcoma (DIC)

Hyperproteinemia causes what

multiple myeloma

Definitive diagnosis of neoplasia can usually be made with

histologic or cytologic examination

Cells are evaluated for

features of malignancy

What are features of malignancy

• Abnormal morphologic features

• High mitotic index

• Abnormal (atypical) mitosis

• High nuclear-to-cytoplasmic (N:C) ratio

• Evidence of invasion or metastasis

What is Abnormal morphologic features

 Anisocytosis, pleomorphisms, anisokaryosis, hyperchromatic or irregular nuclei, and prominent or multiple nucleoli

What is High mitotic index

An increased average number of mitotic figures per 10 high power (400x) fields

What do we mean by High nuclear-to-cytoplasmic (N:C) ratio

 Nuclei that are disproportionately large compared to their cytoplasm

What is evidence of invasion or mtastasis

 Tumor cells breaching normal tissue boundaries, vascular invasion, or present at a site distant from the primary mass

What is immunohistochemistry

• Staining technique that uses antibodies to detect specific cell markers

• Color change with positive immunoreactivity (usually brown or red)

Why do we use special histochemical stains

• Staining technique to highlight specific substances

What is clonaity assays

• Molecular assay that can determined whether a population of lymphocytes is clonal (derived from a single transformed cell) or polyclonal

Why do we use PCR for tumor diagnosis and prognosis

• Lymphoid population has a single rearrangement,

• proliferation is clonal and most likely neoplastic

• Lymphoid population has multiple different receptor rearrangements,

• proliferation is polyclonal and most likely hyperplastic

Why do we use grading in tumor grading and surgical margins

• Provides some indication about biologic behavior of the tumor

What are the common grading for tumor grading and surgical margins

 Differentiation

 Mitotic index

 Tumor necrosis

 Degree of invasiveness

What is a surgical margin

• Evaluated by the pathologist for the presence or absence of tumor cells

Margins can be inked by

histotechnicians

Clinician can add sutures to note what

denote a particular margin