Neoplasia p. 220 First Aid

 

 

  1. Bone and cartilage tumors (osteosarcoma, giant cell tumor, Ewing's sarcoma) - Robbins p. 1236-1245

 

o      Osteosarcoma = malignant tumor producing bone matrix

a.      most common primary malignant tumor of bone, excluding myeloma and lymphoma

b.     Think of 16 y.o. male with a large, swollen knee

c.      Develop at sites of greatest bone growth, where bone cell mitotic activity is at its peak

                                                              i.     Metaphysis of long bones

d.     Gross = big bulky tumors, areas of hemorrhage and cystic degeneration, destroy overlying cortex and produce a soft tissue mass

e.      Clinical Course = present as painful and progressively enlarging masses

f.      Metastatic spread via bloodstream

g.     X-ray = Codman's triangle = triangular shadow between the cortex and raised ends of periostium

o      Giant cell tumor = osteoclastoma = uncommon, benign but locally aggressive neoplasm containing a profuse amount of multinucleated osteoclast type giant cells - think monocyte/macrophage lineage    (p. 233 First Aid)

a.      Arises in 20s-40s

b.     Gross = large, red-brown, cystic degeneration

c.      Histo = uniform oval mononuclear cells that have indistinct cell membranes and appear to grow in a syncytium, frequent mitoses, many osteoclast-type giant cells with 100+ nuclei similar to the nuclei of mononuclear cells

d.     Clinical course = adults - epiphyses and metaphyses; children - metaphysis

                                                              i.     Majority around knee

                                                               ii.     Complains of arthritic=type symptoms

e.     X-ray = large, purely lytic, eccentric, and erode into the subchondral bone plate (fig 28-38)

o      Ewing's sarcoma = primary malignant small round cell tumor of bone (p. 233 First Aid)

a.      Difficult to diagnose because resembles many other tumors

b.     Displays a neural phenotype = expresses oncogene c-myc and chromosome translocation    (11, 22)

c.      Second most common primary malignant bone tumor, youngest age of presentation

d.     Characteristic "onion-skin" appearance in bone

 

  1. Clinical features of lymphomas (Burkitt's and other non-Hodgkin's lymphomas (NHL)) -        Robbins p. 662-663
    1. Burkitt's lymphoma

                                                     i.     Mainly affect children/young adults & account for 30% of childhood NHLs in U.S.

                                                      ii.     Aggressive, but responds well to short-term high-dose chemotherapy, high cure rate

                                                        iii.     Most manifest in extranodal locations

1.     endemic African Burkitts = mass in the mandible + abdominal viscera (kidneys, ovary, adrenals)

2.     nonendemic Burkitts = abdominal mass involving the ileocecum and peritoneum

    1. Non-Hodgkin's lymphomas (Robbins p. 651 and on)

                                                     i.     2/3 present with nontender nodal enlargement that may be localized or generalized

                                                      ii.     1/3 present at extranodal sites (skin, stomach, brain)

                                                        iii.     spread of NHL is less predictable than HL, so staging in NHL is good for prognosis, not treatment - does not spread via contiguous lymph nodes like HL

                                                       iv.     adults = follicular lymphoma, large B cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and multiple myeloma

                                                      v.     children = acute lymphoblastic leukemia/lymphoma and Burkitt lymphoma

                                                       vi.     frequently has a leukemic or blood-borne phase

                                                         vii.     no constitutional symptoms present like in HL

 

 

  1. Risk factors for common carcinomas (lung, breast)
    1. Lung carcinoma (Robbins p. 741-742)

                                                     i.     Tobacco smoking

                                                      ii.     Radiation

                                                        iii.     Asbestos exposure

                                                       iv.     Nickel, chromates, coal, mustard gas, arsenic, beryllium, and iron exposure

    1. Breast carcinoma (Robbins p. 1105-1106)

                                                     i.     Increasing age

                                                      ii.     Proliferative breast disease

                                                        iii.     Carcinoma of the contralateral breast or endometrium

                                                       iv.     Readiation exposure

                                                      v.     Early menarche and late menopause

                                                       vi.     Nulliparity

                                                         vii.     > age 30 when have first child

                                                          viii.     postmenopausal obesity

                                                       ix.     exogenous estrogens (HRT) - controversial

                                                      x.     BRCA1/BRCA2 mutation

 

  1. Chemical carcinogens (vinyl chloride, nitrosamines, aflatoxin) and mechanisms of carcinogenesis (initiator vs. promoter) (Robbins p. 306-309)

 

    1. Vinyl chloride can cause angiosarcomas of the liver.  Used as a refrigerant, monomer for vinyl polymers, adhesive for plastics, formerly and inert aerosol propellant in pressurized containers. 
    2. Nitrosamines are formed in the GI tract of humans and may contribute to the production of gastric carcinoma.  They are derived in the stomach from the reaction of nitrostable amines and nitrate used as a preservative, which is converted to nitrites by bacteria.
    3. Aflatoxin B1 is produced by some strains of Aspergillus flavus that thrive on improperly stored grains and peanuts.  Strong correlation between dietary level of this carcinogen and hepatocellular carcinoma. 
    4. Initiation results from exposure of cells to an appropriate dose of a carcinogenic agent; an initiated cell is in some manner altered, rendering it likely to give rise to a tumor.  Initiation alone is not sufficient for tumor formation.  Initiation causes DNA mutations so it is rapid, irreversible, and has "memory."  I think the three listed above are considered initiators of carcinogenesis.
    5. Promoters can induce tumors in initiated cells, but they are nontumorigenic by themselves.  The cellular changes resulting from the application of promoters do not affect DNA directly and are reversible.  Promoters render cells susceptible to additional mutations by causing cellular proliferation

 

  1. Malignancies associated with pneumoconiosis (asbestos, silicosis) (Robbins p. 730-733)
    1. Pneumoconiosis = non-neoplastic lung reaction to inhalation of mineral dusts commonly encountered in the workplace
    2. Asbestos

                                                     i.     Inhalation may lead to bronchogenic carcinoma, mesotheliomas, laryngeal and perhaps other extrapulmonary neoplasms including colon carcinomas

    1. Silicosis

                                                     i.     Caused by inhalation of crystalline silicon dioxide

                                                      ii.     Most prevalent chronic occupational disease in the world

                                                        iii.     No clear association between silicosis and development of cancer

 

Items 6-10

Sources: Robbins and Pathology BRS –Szanto

 

6. AIDs Associated neoplasms

 

            Kaposi’s Sarcoma                                         B-cell Lymphoma

            Most common cancer in Aids pts                     Non-Hodgkins Lymphoma

            Otherwise rare                                                  AIDs pts also have increased

            In AIDs pts almost entirely                              incidence of Hodgkin’s and

            confined to homosexual males                         hepatocellular carcinoma

 

Histo: Spindle cells that form vascular channels          120x increase risk of NHL

            Monoclonal                                                     Commonly extra-nodal (brain) –HHV-8 association

            Mesenchymal cells infected with HHV-8          Body cavities (another rare site)

            Often involves the viscera (GI)                                    (plerura, peritoneum, pericardial)

                                                                                                EBV association

                                                                                   

AIDs defining neoplasms include:        Kaposi’s, NHL (Burkitt’s), primary lymphoma of the brain, and

                                                            Invasive cancer of uterine cervix

Burkitt’s lymphomas include 3 subtypes: Endemic African, Sporadic, and Aggressive AIDs type

            Subtypes differ in: genotype, clinical course, and viral assoc but are histologically identical.

           

 

7. Pituitary Tumors and other sellar lesions

            Prolactinoma                                                 Craniopharyngioma

            Most common pituitary tumor                         aka ADAMANTINOMA

            In women results in amenorrhea,                      Benign, childhood tumor

            galactorrhea, infetility                                     Derived from Rathke’ pouch

            Caused by lesions or drugs                                 Not a true pituitary tumor

            (methyl-dopa, reserpine, estrogen )     

            Drugs interfere with PIF and prl is                    Nests of squamous cells in loose stroma

                        not inhibited                                        Resembles tooth bud enamel

            Stains chromophobic                                        Often cystic with papillary projections

                                                                                    Calcifications are evident on x-rays

                                   

                                                                                    Kids present with growth retardation

                                                                                    Adults with vision problems                                                                

Other pituitary tumors (acct for 10% of intra-cranial tumors and are monoclonal) include:

1.     non secreting adenomas – mass effect related symptoms (in this case “stalk effect”)

2.     secreting adenomas (symptoms depend on hormone secreted )

ACTH/corticotropic adenoma

GH/somatotropic adenoma

 

8. Tumors of the mouth, pharynx, and larynx

            Vocal cord tumors in smokers

 

1.     Mouth:

Benign              Leukoplakia                             Odontogenic                              Oral cancer

Papilloma –                    Irreg white mucosal                      Odontoma                                  Sq cell carcinoma

  Most common patches                                         Hamartoma derived                   Tongue involved in

  benign epithelial            Due to hyperkeratosis                      from odontogenic epi    more than 50% cases

  tumor                          secondary from                Most common                            Associated with:

                        chronic irritation              odontogenic tumor                      pipe smoking

Fibroma –                      Usually benign                                                                chewing tobacco

  Results from                 May be dysplastic or                                                                    betel nuts

  chronic irritation            carcinoma in situ                                                             EtOH (alcohol)

 

Hemangioma                                                                  Ameloblastoma

  tongue, lip, buccal                                                         aka Adamantinoma

  mucosa                                                                        Epithelial tumor arising

    

Epulis                                                                           from precursor enamel cells

  Any growth of the                                                         Site: mandible

  ginvivae                                                                       Age: before 35

  Usually from healing                                          Benign but can expand jaw

  no tfrom neoplastic process

 

 

2.     Pharynx

3.     Larynx

Singer’s nodules                         Papilloma                              Squamous cell carcinoma

Small, benign polyp              Benign neoplasm             Most common malignant tumor of

Due to chronic irritation                      Site: TRUE vocal cords    larynx

such as excessive use              In adults usually single     Pt: men over 40 yo

of voice                                           and becomes malignant     Assoc with combo of smoking

Associated most                                In kids, many lesions                   and EtOH (alcohol)

commonly with heavy                        and assoc with HPV

smoking                                                                                          Glottic carcinoma

Site: TRUE vocal cords                                                                      arises from true vocal cords

                                                                                                      Most common, best prognosis

                 

                                                                                                      Supraglottic & subglottic carcinomas

                                                                                                      Less common, poorer prognoses

9. Modes of spread of certain cancers

            Renal cell carcinoma        often involves renal vein or vena cava - HEMATOGENOUS              

Stomach carcinoma          aggressive, Local Extension (adjacent organs and peritoneum) and

                                    early Lymphatic spread to nodes and liver

Breast carcinoma Lymphatic to axillary nodes

Lung carcinoma

            Mets to lung       more common than bronchogenic

            Bronchogenic      Local Extension into pleura, pericardium, and ribs

Transitional cell carcinoma (urinary tract) – Local Extension to surrounding tissues

            Prostatic Adenocarcinoma – Hematogenous, bone

            Cervical sq cell carcinoma – Local Extension to vulva

 

10. Clinical features of leukemias (def’n: malignancy of either lymphoid or hematopoietic cell origin)

 

Acute Leukemias

            Characterized by a lot of blasts in the bone marrow and peripheral blood

            Occur more often in children (most common malignancy of pediatric age group)

            2nd incidence peak = >60yo

            Frequently associated with cytogenentic abnormalities (ex. t 9,22 = Philly chromosome bad

prognosis when associated with an acute leukemia but more often found in CML)

            Untreated the course: anemia, leukemia, hemorrhage, and death (within 1 year)

           

            ALL (acute lymphoblastic leukemia)                                  AML (acute myeloblastic leukemia)

            Lymphoblasts predominate                                                aka acute granulocytic leukemia

            Occurs in children                                                           or acute non-lymphoblastic leukemia

            Most responsive to therapy of the acute leukemias     Myeoloblasts and pro-myeloblasts present

            Subgroups classified based on                                Occurs in adults

morphology                                                        Poor response to treatment

Ag-cell surface markers                             Subgroups classified based on

T cell receptor genes                                                         morphology

Rearrangement of Ig heavy chain                            cytochemical characteristics

 

Chronic Leukemias

            Proliferations of lymphoid or hematopoietic cells (more mature forms)

            Longer, less devastating clinical course than acute leukemias

 

            CLL (chronic lymphocytic leukemia)                                  CML (chronic myelogenous leukemia)

            Neoplastic lymphoid (B cells) predominate              aka chronic granulocytic leukemia

            Widespread (blood, LN, spleen, liver, other organs)   Neoplastic clonal growth of myeloid stem

            Leukemic cells can’t make antibodies                                  cells – myeloproliferative syndrome (MPS)

            Occurs more commonly in men over 60 yo               Precursors of rbcs, granulocytes, and platelets

                                                                                                Peaks 35-50yo

                                                                                                Philly Chromosome reciprocal t9, 22

                                                                                                Hybrid bcr-abl  (increased tk activity)

chromo9 proto – oncogene abl fuses with oncogene bcr

 

Cells     Resemble mature peripheral blood lymphos              Leukocytosis- count varies 50,000–200,000

            Smudge cells apparent on slides                             Middle to late myeloid precursors

            peripheral white cell count varies 50,000–200,000 ul             metamyeolcytes

            diffusely infiltrate bone marrow                                          myelocytes

                                                                                                            bands

                                                                                                            segmented forms

Decreased leukocyte Alk Phos in cancer cells

           

Complications    Warm Ab autoimmune hemolytic anemia    

                        Hypo-gammaglobulinemia (early in course)

                        Increased susceptibility to bacterial infxn

 

Course               Indolent                                                 Prominent splenomegaly

                        Lymphadenopathy and                              Hepatomegaly and lymphadenopathy

                        Hepatosplenomegaly                                            Terminates in accelerated phase

Mean survival 3-7 yrs                                                       “BLASTIC CRISIS”

                        Treatment is supportive and does not delay death      blast cells and promyelocytes