MMB (035) Bone and Soft tissue tumours I Flashcards
What is metaplasia ?
an adaptive, reversible change in which one adult “mature, differentiated” cell type is replaced by another of the same category (epithelial or mesenchymal).
What is dysplasia ?
A non-neoplastic, disordered epithelial cell proliferation ;
• Low-grade changes may be reversible
• High-grade dysplasia is premalignant
Cause of Dysplasia ?
Chronic irritation ;
Examples:
-Chronic cervicitis → cervical dysplasia
-Bilharzial Cystitis → urothelial dysplasia
Microscopic features of Dysplasia ?
Atypia + loss of normal orientation “polarity”
Features of atypia ?
- Pleomorphism
- Hyperchromatism
- Increased N/C
- Increased mitosis
Comment on this epidermal slide
Abnormal epidermis with irregular scattering of keratinocytes showingloss of polarity
Grades of Dysplasia ?
Atypia& loss of polarity ;
-Mild: epidermal lower 1/3
-Moderate: 2/3 of epidermis
-Severe: whole epidermal thickness
Neoplasia ?
-an acquired abnormality in which there is abnormal, uncoordinated and excessive cell growth
-persists after the initiating stimulus has been removed (autonomous)
-involves genetic alterations in the neoplastic cells
Detailed definition of Neoplasm ?
A neoplasm is a persistent, abnormal mass of tissue, the growth of which exceeds & is uncoordinated with that of the normal tissue and persists in the same manner after cessation of the stimulus that evoked it.
: The suffix …..oma = neoplasm
Main 2 components of neoplasms ?
- Transformed, neoplastic cells
- Supporting stroma: connective tissue & blood vessels.
Tumor vascularization is affected by (cells) :
- Tumor cells
- Inflammatory cells
Both
» (secrete) tumor- associated angiogenic factors
Compare between malignant and benign tumors accoriding to :
-invasion
-localization
- growth rate
- resemblance to parent tissue
Mode of growth for solid tissue benign tumors ?
Mode of growth for solid tissue surface tumors ?
Non-encapsulated benign tumors include:
-leiomyomas
- hemangiomas
-lymphangiomas
-nevi
-benign surface epithelial tumors
Cell morphology of Benign tumors ?
a. Tumor cells mimic cells of original tissue.
b. Cells are small, uniform in size and shape.
c. N/C is preserved.
d. Mitotic figures are minimal and normal.
Benign Tumor architecture ?
a. Same histological pattern as tissue of origin
b. Well- developed vascular stroma
A major Effect of benign tumors on neighbouring tissue ?
compress neighboring tissue»_space; atrophy
Comment on the possibility of benign tumors recurrence
No recurrence if totally excised
Ways by which a mass neoplasm can be described ?
-Hard
-Fixed
-Irregular
-Ill-defined
Ways by which a surface neoplasm can be described ?
- Polypoid
- Ulcerative mass
- Infiltrative
Anaplasia ?
lack of differentiation
Steps by which a tumor starts invasion ?
1.Detachment of Tumor cells
2.Attachment of cells to matrix components
- Degradation of extracellular matrix
- Migration of tumor cells by chemotactic factors
Mechanisms of distant spread of malignant tumors ?
• Lymphatic
• Hematogenous
• Transcoelomic
• Transluminal
• Implantation
A method of local tumor spread with direct affection on nerves ?
Perineural spread: Spread along perineural space compression»_space; severe pain.
Define Metastasis
development of secondary malignant implants not continuous with the primary tumor.
Do all malignant tumors metastasize ?
Though all malignant tumors undergo local spread, some do not give distant metastasis»_space; LOCALLY MALIGNANT TUMOURS
Lymphatic spread is more common in (carcinoma/sarcoma)
carcinoma
Two ways of lymphatic spread:
- Lymphatic embolism
- Lymphatic permeation
Explain Lymphatic embolism metastasis
Explain Lymphatic permeation metastasis
• Tumor grows as solid cords within lymph vessels causing obstruction of lymph flow»_space; localized edema.
Lymph Node Metastasis Gross ?
Lymph Node Metastasis
• Gross: lymph nodes are:
- enlarged
- firm
Microscopic appearance of matastatic cells ?
Metastatic tumor resembles the primary Tumor ;
(red arrows point to gross and microscopic picture of a lymphoid tissue// yellow arrows point to metastatic infiltration)
Two ways of Hematogenous metastasis ?
1) Direct ; through invasion of basement membrane»_space; enters blood vessels
2) Indirect ; lymphatic spread»_space; Thoracic duct »_space; pulomanry artery
Primary organs that send veinous metastatic emboly ?
- Tumors of organs drained by systemic veins ;
Bone and kidneys
Primary sites where veinous metastatic emboly rest ?
Through which veins can metastatic emboli reach the vertebral system ?
Through :
-Thoracic veins
-Abdominal veins
-Lumbosacral veins
Metastatic tumors(e.g. from lungs, thyroid & breast)usually cause osteolytic/blastic lesions
osteolytic ; osteoclastic bone resorption
prostatic adenocarcinoma metastasis to bone usually cause osteolytic/blastic lesions
osteoblastic bone formation
Bone metastasis in vertebrae, ribs, sternum, pelvis, skull, and ends of long bones ; develops in white/red marrow , causing ….(anemia)
red marrow ; causing pancytopenia
How does an organ invaded with metastatic deposits look like?
• Gross: multiple, well-defined, non-encapsulated nodules
• Cut section: grayish- white nodules
• Microscopic: as the primary tumor.
Define Trans-coelomic spread and give an example
(spread through body cavities)
What do you see ?
And diagnose the abnormality
Dense, compact bone and broad trabeculae of mature bone ;
Osteoma (benign)
Age preferance of Osteoma ?
More frequent in middle- aged males.
Investigate the imaging , point to the lession and give possible diagnosis
Osteoma (benign)
osteogenic sarcoma ?
A malignant mesenchymal tumor characterized by the production of osteoid or bone by malignant tumor cells.
Main sites of Osteosarcoma ?
metaphyseal end of long bones (predominantly the femur, humerus and tibia)
Age prevalence of Primary osteosarcoma ?
Predominantly affects males younger than 20 (before the epiphyses have been closed).
Secondary osteosarcoma ?
on top of a preexisting bone pathology e.g. chronic osteomyelitis, infarcts and fractures of bone.
…. is a strong predisposing factor of Secondary osteosarcoma
Bone irradiation
Local Presenting symptoms of Osteosarcoma ?
Pain and swelling of the affected region
give diagnosis and comment on the findings
Osteogenic sarcoma ;
• Bone destruction with penetration of cortex
• Lifting of the periosteum presents as Codman’s triangle
• Infiltration of adjacent soft tissues
• Spicules of bone arise from the periosteum around the tumor perpendicular to the shaft giving a “Sun- ray, sun-burst, hair on end” appearance
comment on the gross picture
Large grayish-white mass with wide areas of hemorrhage and necrosis.
> > Osteosarcoma
Figure shows gross sample of Osteosarcoma lesion ; can you see codman’s triangle ?
What’s Codman’s triangle ?
Periosteal reaction may appear as the characteristic Codman triangle ; Extension of tumor through the periosteum
Three histological patterns by which bone malignancy can present ?
-Osteoblastic
-Chondroblastic
-Fibroblastic
Describe microscopy of osteosarcomas
The tumor consists of malignant spindle shaped cells with areas of osteoid rimmed by malignant cells. Cells are pleomorphic with hyperchromatic, irregular nuclei and abundant mitoses. Multinucleated giant cells are seen most often near zones of necrosis and calcification. Malignant cartilaginous foci may be present.
comment on microscopy and diagnose
-Tumor cells are present in lacunae and arranged in lobules.
-Osteoid matrix is seen on the lower right of the image.
Diagnosis:
Chondroblastic osteosarcoma
comment on microscopy and diagnose
What is the prognosis (likely course) of osteogenic sarcoma?
Bad prognosis Early metastasis to lungs and bones.
The 5-year survival rate is 5-20%.
Radiation therapy has proven ineffective.
5-year survival rate of osteosarcoma ?
5-20%.
To what extent is has Radiation therapy proven effective in treating osteosarcoma ?
Radiation therapy has proven ineffective.
Figure shows abnormal growth lesion ; diagnose
Benign: Chondroma (Enchondroma) ;
• A benign tumor composed of mature hyaline cartilage
• It can be either solitary or multiple
Comment on gross picture and define what it is
• Well defined, capsulated mass
• Lobulated in shape
• Cut section: bluish and translucent
• Firm in consistency with sharp borders
—Diagnosis : Chondroma
investigate the microscopy and mention what the symbols stand for
-fibrous septa (F) divide the tumor into ;
-lobules (L) of cartilage (hyaline matrix and cartilage cells inside lacunae).
-Cartilage cells (chondrocytes) are rounded with vacuolated cytoplasm. They are arranged singly or in groups
—Diagnosis : Chondroma
investigate the microscopy and mention what the symbols stand for
-fibrous septa (F) divide the tumor into ;
-lobules (L) of cartilage (hyaline matrix and cartilage cells inside lacunae).
-Cartilage cells (chondrocytes) are rounded with vacuolated cytoplasm. They are arranged singly or in groups
—Diagnosis : Chondroma
Comment on x-ray and give a possible diagnosis
Chondroma ;
Localized, radiolucent defect Lobulated with bony expansion
What’s Chondrosarcoma ?
malignant cartilaginous tumor
Age prevalence of Chondrosarcoma ?
age of 30-60
Gender prevalence of Chondrosarcoma ?
male to female ratio is 3 : 1
De novo Chondrosarcoma arrises in ….(%)& of tumors
75%
….(%) of chondrosarcoma arise on top of non-malignant endochondromas
25%
Gross picture illustrates chondrosarcoma samples , Comment , and on the expected consistency
Gross: Firm, grayish- white mass, variable in size.
-Cut section resembles that of cartilage with foci of calcification, cysts and necrotic areas.
What do you see ? And give possible diagnosis
Radiographs of pelvis show a large exophytic growth (G) arising from right iliac bone with chondroid matrix (rings and arcs of calcification).
Radiographic chondroid matrix ?
rings and arcs of calcification
General Clinical picture of Chondrosarcoma ?
Local swelling and pain
Prognosis of Chondrosarcoma ?
Slowly growing tumor, can remain locally aggressive for many years with a high tendency to recur after excision and implant in soft tissues.
Chondrosarcoma’s tendancy of reccurance ?
High tendency to recur after excision
Chondrosarcoma’s respective 5-years survival rate for : grades I, II, III ?
90%, 81%, 43%
CASE STUDY: An autopsy specimen of a 52 year old man who was complaining of progressive pain and swelling at the left pelvic region for many years.
What do you see ?
CASE STUDY: An autopsy specimen of a 52 year old man who was complaining of progressive pain and swelling at the right pelvic region for many years.
What do you see ?
Another name for Osteoclastoma ?
Giant cell tumor
Define Giant cell tumor (Osteoclastoma)
A locally aggressive bone tumor characterized by the presence of multinucleated osteoclast- like giant cells.
Age preference of Giant cell tumor (Osteoclastoma) ?
20-55 years of age (after epiphyseal closure)
Common sites of Giant cell tumor (Osteoclastoma) ?
Nearly always within the epiphysis and extends to metaphysis, 50% about the knee; distal femur, proximal tibia or proximal fibula, but virtually any bone can be involved.
comment on gross picture and diagnose
Clinical presentation of Giant cell tumor (Osteoclastoma) ?
-Deep, persistent intraosseous pain within the knee
-Reactive knee effusion is the initial symptom in about 1/3 of patients
-Pathological fracture
comment on radiography and diagnose
Well-defined lytic lesion that involves the metaphysis and epiphysis is typical of a giant cell tumor
typical x-ray presentation of giant cell tumor ?
Well-defined lytic lesion that involves the metaphysis and epiphysis is typical of a giant cell tumor
comment on radiography and diagnose
• Lytic lesion with characteristic soap- bubble appearance
-Well-defined lytic lesion , that involves the metaphysis and epiphysis is typical of a giant cell tumor
stage I of Giant cell tumor ?
- latent benign giant cell tumors
- no local aggressive activity
stage II of Giant cell tumor ?
- benign active GCT
stage III of Giant cell tumor ?
- locally aggressive tumors
- imaging studies demonstrate a lytic lesion surrounding medullary and cortical bone
- there may be indication of tumor penetration through the cortex into the soft tissues
The two cell components of Osteoclastoma microscopy ?
-Oval, mononuclear cells with variable mitosis.
-Scattered osteoclast type giant cells ( with>100 nuclei)
There are areas of hemorrhage and necrosis as well.
Another name for Peripheral neuroectodermal tumour [PNET] ?
Ewing’s Sarcoma
Define Ewing’s Sarcoma
A primary malignant tumor , believed to originate from undifferentiated mesenchymal cells within the medullary cavity of neuroectodermal origin
Age prevalence of Ewing’s Sarcoma ?
10-20 years of age
Gender prevalence of Ewing’s Sarcoma ?
slight male predominance.
Describe the aggressiveness of Ewing’s Sarcoma
highly aggressive with a potential blood spread to any organ
Site of Ewing’s Sarcoma ?
-Originates in the medullary cavities of predominantly long bones, although any bone can be involved.
-Extra-skeletal Ewing’s sarcoma may also occur
Comment on Gross Picture and give possible diagnosis
The tumor mass is greyish-white, showing destruction of the medullary cavity by hemorrhage and necrosis, extending into the cortex and adjacent soft tissues
-Ewing’s sarcoma
(Primitive or peripheral neuro-ectodermal tumor (PNET))
Figure illustrates microscopy of a bone tumor , comment and diagnose
-The tumor is composed of sheets or cords of undifferentiated small round cells larger than lymphocytes.
-Cells have a scanty cytoplasm rich in glycogen.
Diagnosis : Ewing’s Sarcoma ;
(Peripheral neuroectodermal tumour) [PNET]
clinical presentation of Ewing’s sarcoma ?
• Painful, enlarging mass in diaphysis of long bones and pelvic flat bones.
• Sometimes associated with fever,
↑sedimentation rate and leukocytosis»_space; condition may thus be mistaken for osteomyelitis.
A bone tumor commonly mistaken for osteomyelitis ?
And why ?
Ewing’s sarcoma
Primitive or peripheral neuro-ectodermal tumor (PNET) :
- due to it’s microscopy resembling large lymphocyte like cells , and increased ESR and leukocytes in CBC
Figure illustrates plain radiography of a bone tumor , diagnose the tumor and comment on it’s x-ray findings
Mention an example of Tumours of skeletal muscles
Rhabdomyoma
Common site for Rhabdomyoma ?
the heart
….Is the common soft tissue sarcoma in children & adolescents <20y
Rhabdomyosarcoma
common sites Of Rhabdomyosarcoma ?
• Head and neck
• Urinary tract
Rhabdomyosarcoma has/doesn’t have a Genetic background
Has a Genetic background
diagnose the tumor using the gross picture
Rhabdomyosarcoma
Parent cell of Rhabdomyosarcoma ?
RHABDOMYOBLASTs
Behaviour of Rhabdomyosarcoma ?
Aggressive
Management of Rhabdomyosarcoma ?
-Combined “limb-sparing surgery, chemotherapy and radiotherapy”
-Outcome of management: better in children than adults